Enteric‐coated mycophenolate sodium in the treatment of refractory pemphigus

Background One of the major goals of pemphigus therapy is to reduce the patient’s cumulative exposure to systemic corticosteroids. To investigate the efficacy of enteric‐coated mycophenolate sodium (EC‐MPS), 10 patients with active, refractory pemphigus vulgaris (PV) or foliaceous (PF) were treated with EC‐MPS (1440 mg daily) and prednisone (75 mg daily) over 18 months. Observations Following EC‐MPS/prednisone therapy, disease progression was inhibited between days 30 and 45 in 9/10 patients (8 PV; 1 PF). At 18 months, 8/9 PV patients had clinically quiescent disease; EC‐MPS therapy was no longer required in two patients as a result of disease remission. The remaining PV patient showed no response to treatment. The PF patient also had clinically quiescent disease but with high levels of anti‐desmoglein‐1. ECMPS dose was reduced to 720 mg daily in 4/9 patients by month 6. Average daily prednisone requirement decreased to 25 mg at 6 months and to 15 mg at 18 months. Three adverse events were reported: headache (two cases; one mild and one moderate) and significant increase in blood glucose (one case; moderate). Conclusions Enteric‐coated mycophenolate sodium is effective and safe as an adjuvant therapy in patients with refractory pemphigus and may be effective even in patients whose disease is unresponsive to azathioprine.     

A 6‐year treatment experience for pemphigus: retrospective study of 69 Chinese patients

There is a lack of data on treatment and prognosis of pemphigus in China. The aim of this study was to evaluate long‐term follow‐up and prognosis of pemphigus. Forty‐seven inpatients with pemphigus vulgaris (PV) and 22 with pemphigus foliaceus (PF) were recruited in this retrospective study. The average age at onset was 51.6 and 54.9 years in PV and PF, respectively. High‐dose systemic steroids were administered in 47 PV and 21 PF, of which 18 PV and 8 PF with adjuvant therapies. CD4 lymphocytopenia was found in 5 PV and 2 PF patients at admission and successfully treated by intravenous thymopentin daily. During a mean follow‐up of 37.1 months, 41 PV and 19 PF reached remission, 30 PV and 9 PF relapsed, 4 PV and 2 PF died. Major causes of death were relapse of pemphigus due to discontinuation of oral steroids by the patients themselves (four cases) and severe infections (two cases, one with severe CD4 lymphocytopenia). The 1‐year mortality rate of PV and PF was 8.5% and 4.5%, respectively. Cox regression analysis indicated that age at onset of pemphigus was an independent risk factor related to the elevated mortality. Our report confirmed the high mortality rate of pemphigus in a Chinese population and stressed that patient education was urgently needed to prevent relapses and deaths.     

Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil

BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid-sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the effectiveness of mycophenolate as adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study. SETTING: University hospital. PATIENTS: The study included 42 consecutive patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus foliaceus) who had relapses during prednisone taper or had clinically significant adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22 (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus, respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively. The median time to achieve complete remission was 9 months (range, 1-13 months). The treatment was administered for a median of 22 months, and the median follow-up period was 22 months. Seventy-seven percent of patients had no adverse effect. Two patients had side effects severe enough to necessitate discontinuation of treatment, one because of symptomatic but reversible neutropenia and the other because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in the treatment of both pemphigus vulgaris and pemphigus foliaceus.     

Short-time extracorporeal photochemotherapy in the treatment of drug-resistant autoimmune bullous diseases.

BACKGROUND: Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are potentially severe diseases. In drug-resistant PV and pemphigus foliaceus, long-term adjuvant treatment with extracorporeal photochemotherapy (photopheresis, ECP) has been reported to induce remission. Only limited numbers of patients have been reported so far. No information about the effectiveness in drug-resistant BP is available. PATIENTS AND METHODS: Seven patients with drug-resistant autoimmune bullous diseases have been referred to the photopheresis center of Jena (3 x PV, 3 x BP, 1 x pemphigus foliaceus). The age ranged from 31 to 85 years. ECP was performed on 2 consecutive days once a month. Oral 8-methoxypsoralen was used as photosensitizer. Previous immunosuppressive treatment with either prednisolone or prednisolone/ azathioprine was continued. RESULTS: Complete remission (absence of skin or mucous membrane lesions) was achieved in the 6 patients with PV and BP after 1-4 cycles. In the patient suffering from pemphigus foliaceus, a partial remission (> 50% improvement) was observed; in all except this patient, the immunosuppressive treatment could be tapered. Long-term remission was achieved. No severe side effects were observed. The treatment was well tolerated. CONCLUSIONS: Short-time ECP is an effective and safe adjuvant treatment for patients with drug-resistant autoimmune bullous diseases. It can induce remission and allows dose tapering of the immunosuppressive drugs.     

Evaluation of cyclophosphamide pulse therapy as an adjuvant to oral corticosteroid in the management of pemphigus vulgaris

Corticosteroids are the mainstay of treatment for pemphigus. However, despite the introduction of adjuvant therapy for PV, the mortality rate has remained static over the past 2 decades, and consequently, a new adjuvant therapy that is both safe and effective is needed. Intravenous pulse cyclophosphamide has shown encouraging results in few studies, with a better safety profile than the oral formulation, and with better treatment compliance. We undertook a randomized, prospective, non‐blinded trial to assess the efficacy of cyclophosphamide pulse therapy (CPT) as an adjuvant to oral corticosteroid in pemphigus vulgaris (PV). We enrolled 60 patients with mild to moderate active disease to receive either daily oral prednisolone or intravenous CPT prednisolone for 1 year, and they were then followed up for another year. At the end of the study period, the time taken to initiate response was similar in both groups, but in the group who received pulse cyclophosphamide, there was a reduced time to remission, a greater proportion of cases who achieved remission, a lower number of patients who relapsed while on treatment or after stopping treatment, and a lower cumulative dose of corticosteroid. Hence, the overall trend was in favour of CPT, although this was not significant. CPT also had a good safety profile. Based on the results of this trial, CPT may be a useful adjuvant in PV in terms of reducing time to remission, relapse rates and cumulative dose of steroid, and it has a good safety profile.     

Efficacy and Safety of Cyclophosphamide, Azathioprine, and Cyclosporine (Ciclosporin) as Adjuvant Drugs in Pemphigus Vulgaris

Background:Pemphigus vulgaris is a potentially life-threatening, autoimmune bullous disease of the skin and mucous membranes. Most commonly, the disease is treated with prednisone in combination with an immunosuppressant agent, frequently referred to as adjuvant drug. However, there is no consensus regarding the first-choice adjuvant drug for the treatment of pemphigus vulgaris or the recommended dosage. Objective:To evaluate the efficacy and safety of prednisone as monotherapy and in combination with the three most popular adjuvant agents — azathioprine, cyclosporine (ciclosporin), and cyclophosphamide in the treatment of pemphigus vulgaris time to immunologic remission (non-detectable circulating pemphigus vulgaris antibodies), proportion of patients who remained free of clinical relapse within 5 years after discontinuation of therapy, time from treatment discontinuation until first relapse, and incidence of adverse effects. Results:The average (± SD) time to clinical remission was 7.2 ± 13.1 months in patients who received prednisone monotherapy, 6.8 ± 10.5 months in patients receiving additional azathioprine, 8.1 ± 11.8 months in the cyclosporine group, and 4.9 ± 6.9 months (which was significantly shorter than all other treatment groups, p < 0.05) in patients receiving cyclophosphamide. The average (± SD) times to immunologic remission were 33 ± 27 months, 28 ± 24 months, 30 ± 21 months, and 23 ± 17 months for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. The proportions of patients who remained free of clinical relapse within 5 years after discontinuation of therapy were 55%, 50%, 43%, and 69% for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. In patents who experienced relapse, the average (± SD) time from treatment discontinuation to clinical relapse was 10.50 ± 6.86 months in patients receiving prednisone monotherapy, 16.40 ± 17.36 months in the azathioprine group, 12.44 ± 6.48 months in the cyclosporine group, and 21.16 ± 20.13 months in the cyclophosphamide group. The safety profiles of all treatment regimens were comparable. Conclusion:Oral prednisone with cyclophosphamide is the most effective treatment for pemphigus vulgaris. All therapy regimens had a similar safety profile. In our opinion, cyclophosphamide at a dose of 1.1–1.5 mg/kg/day should be the adjuvant drug of choice in the treatment of moderate-to-severe pemphigus vulgaris.     

Treatment of Pemphigus

Ninety-eight cases of various types of pemphigus were treated between 1978-1987. Sixty-one cases were pemphigus vulgaris (PV), 22 cases were pemphigus foliaceus, generalized type (PFG) in which one case developed pemphigus vegetans, 11 cases were pemphigus foliaceus localized type (PFL), and four cases were pemphigus erythematosus (PE). Fifteen mild cases of PV and three mild PFG were treated with corticosteroid (prednisolone or prednisone) alone, and dapsone or cyclophosphamide (CP) were added as treatment failed in two cases of each. Dapsone alone was used effectively in three cases of mild PV. Eight cases of moderate and three cases of severe PV, as well as five cases of moderate PFG, failed to respond to corticosteroid alone but were cleared by the addition of CP. Thirty-two moderate cases of PV and PFG treated with a combination of corticosteroid 60 mg/day plus initial CP and 14 severe cases of PV and PFG treated with corticosteroid 120 mg/day plus initial CP, resulted in clearing skin lesions in 2 months. Azathioprine or chlorambucil were substituted in three cases who developed CP toxicity. Addition of gold sodiumthiomalate in six refractory cases when the above regimens failed, caused a complete remission in two and partial control in four. Higher dosage of prednisolone or prednisone more than 120 mg/day has never been used. Eleven cases of PFL and four cases of PE were treated with uneventfully good results. Intercellular antibody titers became negative within 4.67 months except in refractory cases, however, the treatment was continued for at least 3 years. Herpes simplex superimposed infection was more common than herpes zoster infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Low-dose rituximab is effective in pemphigus

Background Rituximab, an anti‐CD20 antibody, was shown in open series studies to be effective in treating pemphigus at a dose of 4 × 375 mg m^?2 as approved for B‐cell malignancies. Objectives We investigated whether a lower dose of rituximab is also effective for pemphigus. Methods Patients with pemphigus were treated with a single course of two infusions of rituximab (500 mg each) at an interval of 2 weeks. Clinical consensus late end points, B‐cell number, desmoglein 1 and desmoglein 3 indices were monitored. Results We enrolled 15 patients in the study: three with pemphigus foliaceus (PF) and 12 with pemphigus vulgaris (PV). The follow‐up was 32–152 weeks (median 94). All 15 patients responded to therapy. Eight patients achieved complete remission in a median period of 51 weeks (four on minimal therapy, four off therapy). Seven patients achieved partial remission in a median period of 34·5 weeks (five on minimal therapy, two off therapy). Relapses (40%) were seen between 53 and 103 weeks (median 97) after start of therapy. B‐cell numbers dropped to < 1% after first infusion, and remained undetectable in patients with sustained remission. The antidesmoglein 1 index correlated well with the clinical severity in PF, but this was less obvious in PV. Conclusions A low dose of rituximab is an effective and safe treatment for pemphigus. Relapses may occur, mostly at the end of the second year. Cost–effectiveness studies with a long follow‐up are required to determine the proper dosage of this expensive drug in pemphigus.     

Therapeutic effect of mizoribine on pemphigus vulgaris and pemphigus foliaceus

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0?μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.     

Pemphigus vulgaris and pemphigus foliaceus: similar prognosis?

BACKGROUND: Pemphigus is a rare, life-threatening, acquired autoimmune bullous dermatosis. The prognosis of pemphigus foliaceus (PF) is usually regarded as more favourable than that of pemphigus vulgaris (PV). Our study aims to compare the clinical course of PV and PF in 37 patients. PATIENTS AND METHODS: We conducted a retrospective study over a period of eight years (1994-2001). The patients were referred during this period and were followed until December 2003. PF and PV were included based on clinical, histological and immunopathological criteria. RESULTS: In our study there was no significant difference between PF group and PV group concerning; age, sex, duration of the disease, presence of disseminated lesions, treatment, healing time, remission, relapse, complications, death and follows up duration. The survival graph showed no difference between the two groups for the first two relapses. There was a tendency to significance concerning an additional treatment and relapses frequency in the PF group. CONCLUSIONS: Few studies in the literature were interested in the evolution of the two forms of pemphigus. They showed that the two populations share the same clinical course; nevertheless they revealed the frequency of partial remission, failed treatment, relapses, necessity of high dose of corticosteroids, and difficulties of discontinuing treatment in PF. Our study, suggests that PF and PV may share the same clinical course.     

Long-term efficacy of dexamethasone-cyclophosphamide pulse therapy in pemphigus

Background: Corticosteroids are used as a daily oral therapy or in a pulse form with or without various adjuvant drugs for the treatment of pemphigus. Our long-term experience with the use of dexamethasone-cyclophosphamide pulse therapy as a first-line treatment modality for pemphigus is presented. Methods: A retrospective analysis of records of pemphigus patients treated by dexamethasone-cyclophosphamide therapy was carried out. The treatment regimen consisted of the monthly administration of intravenous dexamethasone (136 mg) for 3 consecutive days with addition of intravenous cyclophosphamide (500 mg) on the second day. Oral cyclophosphamide (50 mg) daily and oral corticosteroids (low tapering doses) were given in the intervals between the pulses, till partial remission was achieved. Pulse therapy was then continued for another 6 months followed by daily oral cyclophosphamide (50 mg) for 1 year, which produced a complete remission. Results: A total of 36 patients, 32 with pemphigus vulgaris and 4 with pemphigus foliaceus, were treated with this regimen. Two to 8 pulses were required to achieve a partial remission, while the total number of pulses given for complete remission ranged from 8 to 32. The duration of pulse therapy correlated with both the disease severity and the time to achieve remission. All patients are now in complete remission with a follow-up of 0.5-12 years. Four patterns of remission were observed, related to the severity of disease. The response to pulse therapy was faster in the milder form of disease. The severe form of disease required more pulses as well as higher doses of intervening oral corticosteroids. Conclusions: Dexamethasone-cyclophosphamide pulse therapy is an effective form of treatment in pemphigus and results in long-lasting remissions.     

A clinical study of patients with pemphigus vulgaris and pemphigus foliaceous: an 11-year retrospective study (1996-2006)

Only a few reports have been published of detailed clinical studies of pemphigus in Japan. The aim of this study was to determine the clinical characteristics of patients with pemphigus vulgaris (PV) and pemphigus foliaceous (PF), who were newly diagnosed in the dermatology department of Kurume University Hospital, Japan, over the past 11 years. The primary site of involvement was the oral mucosa in 21 patients (75%) with PV. At the initial visit, most of the patients with PV had moderate to severe disease. With regard to management, systemic corticosteroids were the mainstay of treatment for patients with PV, and plasmapheresis was the most frequently used adjuvant therapy. Dapsone was the mainstay of treatment for the patients with PF. The patients were investigated for any association with an underlying malignancy; in patients with PV, lung, stomach and uterine cancers (one patient each) were seen.     

Four mild but refractory cases of pemphigus foliaceus successfully treated with intravenous immunoglobulin

Intravenous immunoglobulin (IVIG) is a potential second line of therapy for pemphigus, with increasing evidence of its effectiveness and safety, although oral corticosteroids remain the first treatment for pemphigus. IVIG is usually applied in severe cases of pemphigus, particularly pemphigus vulgaris (PV). Pemphigus foliaceus (PF) caused by immunoglobulin PF autoantibodies to desmoglein 1 (Dsg1) is usually milder than PV. However, PF cases are occasionally resistant to corticosteroids and require long‐term treatment to control the disease, leading to various adverse effects. IVIG was used in patients with relatively mild PF, who were resistant to therapies with corticosteroids and dapsone. We assessed the disease severity by Pemphigus Disease Area Index (PDAI) and measured anti‐Dsg1 antibody indices by enzyme‐linked immunosorbent assay, before and 4 months after IVIG. Four Japanese female PF patients (57.3 ± 8.6 years) were treated with a single cycle of IVIG (400 mg/kg per day for five consecutive days) in combination with the previous therapies. Within 1–2 months of addition of IVIG, all PF cases showed remarkable improvement of skin lesions, and PDAI also markedly decreased. For 2 years after IVIG, no apparent exacerbation was observed. Anti‐Dsg1 antibody indices decreased in all cases during the 2 years. IVIG could be a potential treatment for not only severe cases of PV but also mild and refractory cases of PF. IVIG may trigger the shift from intractable condition to remission via non‐pathogenic anti‐Dsg1 antibodies or some mechanisms excluding anti‐Dsg1 antibody.     

Pemphigus in Korea: clinical manifestations and treatment protocol

Pemphigus, a rare, chronic blistering disease of the skin and mucous membranes with severe morbidity and occasional mortality, is the most common autoimmune bullous disease in Korea. The purpose of this study was to evaluate the clinical features and propose a treatment strategy for patients with pemphigus. A retrospective analysis was conducted of 51 pemphigus patients seen between 1993 and 2001. Pemphigus vulgaris (PV) was the most common type with 32 cases, followed by 19 cases of pemphigus foliaceus (PF). The male to female ratio was 1:1.3, with females predominating, particularly among PV patients (PV, 1:1.5; PF, 1:1.1). The average ages at onset of PV and PF were 44.3 and 51.0 years old, respectively. Mucosal involvement was noted in 27 cases (84.4%) of PV but in only 3 cases (15.8%) of PF. Most patients initially received relatively low to intermediate doses (0.3-1.0 mg/kg/day) of prednisolone, and 23 (71.9%) PV patients and 10 (52.6%) PF patients also received immunosuppressive agents. Oral prednisolone and azathioprine (100 mg/day) formed the mainstay of treatment for our patients (47.1%). At the time of writing, 25.5% (13/51) of patients are in complete remission, and 72.5% (37/51) are undergoing maintenance therapy. One patient died due to sepsis during the treatment. For the treatment of pemphigus, a course of the lowest possible corticosteroid dosage in combination with immunosuppressive agents appears to be effective and less toxic than a high corticosteroid dosage.     

Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus

BACKGROUND: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are autoimmune blistering skin diseases usually treated with high-dose systemic corticosteroids and other immunosuppressants that may cause severe side-effects. Plasmapheresis also has been demonstrated to be of benefit in the treatment of pemphigus. In contrast to plasmapheresis, staphylococcal protein A immunoadsorption (PA-IA) specifically removes immunoglobulin from the circulation, allows treatment of larger plasma volumes, and does not require the substitution of plasma components. OBJECTIVES: To determine the effectiveness and side-effects of PA-IA in patients with severe pemphigus. METHODS: Five patients with severe pemphigus (PV, n = 4; PF, n = 1) were treated by PA-IA. Three of these patients had been refractory to various treatment regimens. In addition to PA-IA, methylprednisolone, 0.5 mg x kg-1 body weight day-1 was given initially and subsequently tapered. RESULTS: In all patients, a dramatic clinical improvement was seen within 2 weeks after initiation of therapy. Patients were free of lesions after 3, 4, 4, 10 and 21 weeks of treatment, respectively. Concurrently, autoantibody levels decreased rapidly. CONCLUSIONS: PA-IA is a rational, effective, and safe adjuvant therapy for severe pemphigus and warrants wider use for this indication. A controlled study should compare side-effects and effectiveness of PA-IA with other treatment options for pemphigus.     

Adjuvant rituximab treatment for pemphigus: A retrospective study of 45 patients at a single center with long‐term follow up

To evaluate the long‐term outcomes of rituximab in the treatment of pemphigus and the influence of disease duration and different dose of rituximab on the clinical response, 45 patients with refractory pemphigus treated with at least one cycle of two infusions of rituximab (375 mg/m² per infusion weekly) were retrospectively studied. All patients were followed up for more than 2 years. All patients achieved complete or partial remission within 8 months of the first cycle. Thirty‐four (76%) patients relapsed at a median of 17 months. All patients who received additional cycles after relapse achieved new remissions. Early use of rituximab within 1 year of disease duration and high‐dose therapy induced better outcomes, although the results in early use were not statistically significant. Acute respiratory distress syndrome occurred in one patient. Rituximab is effective in treating pemphigus, but relapses are frequent during long‐term follow up, and additional cycles are beneficial in relapsed cases. Early and high‐dose rituximab therapy may be more effective.     

Anti-desmoglein IgG autoantibodies in patients with pemphigus in remission

Background   Desmoglein (Dsg) enzyme-linked immunosorbent assay (ELISA) is a highly sensitive and specific method to detect anti-Dsg3 and anti-Dsg1 IgG autoantibodies in pemphigus vulgaris (PV) and pemphigus foliaceus (PF), respectively. Whereas ELISA index values fluctuate in parallel with disease activity, ELISA positivity during clinical remission has been observed.
Objective   To determine the prevalence of positive Dsg ELISA index values during clinical remission. To ascertain how positive Dsg ELISA scores during remission compare with those during active disease.
Methods   Dsg ELISA was performed on serum samples of PV and PF patients taken during remission (lesion-free ≥ 3 months on ≤ 15 mg or ≤ 5 mg/day prednisolone) and active disease. We used a modified ELISA protocol with optimal serum dilutions in sera with very high initial index values, as we previously described.
Results   When remission was defined as no eruption ≥ 3 months with ≤ 15 mg/day prednisolone, 20 of 43 PV patients (46.5%) and 4 of 12 PF patients (33.3%) showed Dsg3 and Dsg1 ELISA positivity, respectively. With ≤ 5 mg/day, 6 of 17 PV (35.3%) and 1 of 6 PF patients (16.7%) showed Dsg3 and Dsg1 ELISA positivity, respectively. The index value of each ELISA-positive remission serum was consistently lower than that of its corresponding active disease serum. We observed consistent correlation between ELISA index values and indirect immunofluorescence titres.
Conclusions   Circulating anti-Dsg IgG autoantibodies are found in a considerable percentage of pemphigus patients in remission, who have high levels of antibody production during active stages.     

A Case of pemphigus foliaceus which occurred after five years of remission from pemphigus vulgaris

A 77-year-old Japanese female developed pemphigus foliaceus (PF) after 5 years of remission from pemphigus vulgaris (PV). The patient had painful erosions in her mouth and flaccid blisters of the skin and was diagnosed as having PV, which responded well to corticosteroid treatment. She was then free from any lesion of PV for 5 years with a low dose of corticosteroid. Then she developed scaly erythematous lesions on the skin and was diagnosed as suffering from PF. Enzyme-linked immunosorbent assay (ELISA) using recombinant desmoglein 1 (Dsg-1) and Dsg-3 revealed that she had anti-Dsg-3 IgG in the PV stage, no antibodies during remission and anti-Dsg-1 IgG in the PF stage. These findings indicate that the target antigen was shifted from Dsg-3 to Dsg-1 along with the phenotype after a 5-year interval in this patient.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.     

Rituximab in the adjuvant treatment of pemphigus vulgaris: a prospective open-label pilot study in five patients

BACKGROUND: Rituximab is a monoclonal antibody directed against the CD20 antigen expressed on B lymphocytes. There are reports of its efficacy in the treatment of autoimmune diseases, including pemphigus. OBJECTIVES: Prospectively to evaluate the efficacy of rituximab as adjuvant treatment for pemphigus vulgaris (PV). METHODS: Patients with PV were treated with intravenous rituximab (375 mg m(-2)) weekly for 4 weeks in this prospective open-label pilot study. Other concurrent immunosuppression was continued. RESULTS: Of five patients, one achieved complete remission and was able to cease all medication, while two achieved clearance of clinical lesions but continued on systemic therapy. Two patients had progressive disease. Time to response was 2-8 months, with a 13- to 18-month response duration. Response was associated with reduction in serum antiepithelial antibodies. Two patients had significant infectious complications (one developed community-acquired pneumonia associated with delayed-onset neutropenia and the other developed cytomegalovirus infection). CONCLUSIONS: Rituximab has shown efficacy in the treatment of PV. Patients on multiple immunosuppressives should be closely monitored for infectious complications.