Background The assumption that adjuvant modalities have added value to oral glucocorticoids in the treatment of pemphigus is intuitively sound but has not been conclusively proven. Objective We ...sought to compare the efficacy and safety of oral glucocorticoid treatment with or without adjuvants for pemphigus vulgaris and pemphigus foliaceus. Methods We performed a systematic review and meta-analysis of randomized controlled trials. The primary outcome was remission. Secondary outcomes were disease control, time to disease control, relapse, time to relapse, cumulative glucocorticoid dose, withdrawal because of adverse events, and all-cause death. Trials were pooled irrespective of adjuvant type evaluated. Results Ten trials (559 participants) were included. Adjuvants evaluated were azathioprine, mycophenolate mofetil, cyclophosphamide, cyclosporine, intravenous immunoglobulin, plasma exchange, and infliximab; not all were included in every analysis. Although adjuvants were not beneficial for achieving remission, they were found to collectively decrease the risk of relapse by 29% (relative risk 0.71, 95% confidence interval 0.53-0.95). Limitations Different adjuvants were pooled together. Conclusion Adjuvants have a role in pemphigus treatment, at least in reducing the risk of relapse. Further randomized controlled trials of other promising modalities are warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Pemphigus vulgaris (PV) is a mucocutaneous blistering disease characterized by IgG autoantibodies against the stratified squamous epithelium. Current understanding of PV pathophysiology does not ...explain the mechanism of acantholysis in patients lacking desmoglein antibodies, which justifies a search for novel targets of pemphigus autoimmunity. We tested 264 pemphigus and 138 normal control sera on the multiplexed protein array platform containing 701 human genes encompassing many known keratinocyte cell-surface molecules and members of protein families targeted by organ-non-specific PV antibodies. The top 10 antigens recognized by the majority of test patients' sera were proteins encoded by the DSC1, DSC3, ATP2C1, PKP3, CHRM3, COL21A1, ANXA8L1, CD88 and CHRNE genes. The most common combinations of target antigens included at least one of the adhesion molecules DSC1, DSC3 or PKP3 and/or the acetylcholine receptor CHRM3 or CHRNE with or without the MHC class II antigen DRA. To identify the PV antibodies most specific to the disease process, we sorted the data based on the ratio of patient to control frequencies of antigen recognition. The frequency of antigen recognition by patients that exceeded that of control by 10 and more times were the molecules encoded by the CD33, GP1BA, CHRND, SLC36A4, CD1B, CD32, CDH8, CDH9, PMP22 and HLA-E genes as well as mitochondrial proteins encoded by the NDUFS1, CYB5B, SOD2, PDHA1 and FH genes. The highest specificity to PV showed combinations of autoantibodies to the calcium pump encoded by ATP2C1 with C5a receptor plus DSC1 or DSC3 or HLA-DRA. The results identified new targets of pemphigus autoimmunity. Novel autoantibody signatures may help explain individual variations in disease severity and treatment response, and serve as sensitive and specific biomarkers for new diagnostic assays in PV patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-blinded trials of pemphigus vulgaris suggest that mycophenolate mofetil (MMF) may be beneficial. In a prospective, multicenter trial, outpatients with mild or moderate pemphigus vulgaris were ...randomized to MMF (2 or 3gday−1) plus oral corticosteroids or placebo plus oral corticosteroids for 52 weeks. The primary end point was the proportion of patients in the placebo and combined MMF groups responding to treatment (absence of new, persistent oral or cutaneous lesions, and prednisone dose ≤10mgday−1 from weeks 48 to 52). Of 96 randomized patients, 94 were given treatment and 75 completed the study. Treatment responses occurred in 40 of 58 patients (69.0%) in the combined MMF group and 23 of 36 (63.9%) in the placebo group (P=0.6558, 95% confidence interval –17.4 to 27.6). MMF-treated patients showed faster and more durable responses. In post hoc analyses, more patients taking MMF showed sustained responses for 3 or 6 months than did placebo patients. MMF was well tolerated. Although MMF did not show an advantage on the primary end point, there seemed to be a beneficial treatment effect on several secondary end points, including time to response and duration of response. Thus, MMF may be a potentially useful agent in patients with mild or moderate pemphigus vulgaris. JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article please go to http://www.nature.com/jid/journalclub
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background Rituximab is increasingly being appreciated as a remarkably effective treatment for pemphigus, mostly concomitantly with other immunosuppressive medications. The majority of studies have ...used a single cycle of rituximab with the same dosage as approved for the treatment of lymphomas, ie, 375 mg/m2 weekly × 4 weeks. Rituximab is also approved for the treatment of rheumatoid arthritis, with a different dosing regimen: 1000 mg × 2, days 1 and 15. Objective We aimed to assess the clinical response of patients with pemphigus to a single cycle of rituximab at the dosage used in rheumatoid arthritis. We also evaluated the response to repeated cycles of rituximab. Methods A total of 47 patients with pemphigus who were treated with rituximab at a dosage of 1000 mg × 2, days 1 and 15, most with concurrent immunosuppressive medications, were retrospectively studied. Results Remission rates after the first treatment cycle reached 76%. Repeating the treatment further increased the remission rates to 91%. There was a 22% relapse rate at a median time of 8 months, but 75% of relapsing patients achieved remission again with additional cycles. The side-effect profile was similar to previous reports, except for an immediate postinfusion pemphigus exacerbation in 4 patients. Limitations This was a retrospective study with a limited follow-up period. Conclusion The rheumatoid arthritis dosage of rituximab was efficacious and well tolerated in patients with pemphigus. Patients who fail to achieve remission after 1 cycle or patients who relapse seem to benefit from repeated rituximab cycles.
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5.
Paraneoplastic Pemphigus Anhalt, Grant J.
The Journal of investigative dermatology symposium proceedings,
January 2004, 2004-01-00, 2004-Jan, 20040101, Volume:
9, Issue:
1
Journal Article
Peer reviewed
Open access
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Paraneoplastic pemphigus (PNP) has been described as an antibody-mediated mucocutaneous disease occurring almost exclusively in patients with lymphocytic neoplasms. We describe 4 patients with the ...clinical features of the lichenoid variant of PNP in the absence of detectable autoantibodies. On the basis of these findings, we conclude that the spectrum of PNP likely includes patients with disease predominantly or exclusively mediated by cytotoxic T cells rather than autoantibodies. The pathophysiology and range of PNP disease are likely more complex than was initially believed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To evaluate the effectiveness of immunosuppressive drug therapy in the treatment of ocular mucous membrane pemphigoid (MMP).
Retrospective cohort study.
Ninety-four patients with biopsy-proven ocular ...MMP seen at the Pemphigoid Clinic at Wilmer Eye Institute from July 1984 through November 2006.
Data recorded included demographics, use and doses of immunosuppressive drugs, response to therapy, and side effects associated with drug use.
Outcome measures included: (1) ocular control, defined as resolution of inflammation and cessation of cicatrization of the conjunctiva; (2) ocular remission, defined as ocular control for 3 months or more after the cessation of immunosuppressive drug therapy; and (3) ocular relapse, defined as the recurrence of ocular disease in either eye after a remission.
By 1 year of treatment, 82.9% of patients had complete control of the inflammation, and of these, 86.3% achieved a remission at some point during follow-up. The incidences of ocular control, remission, and relapse were 1.03 (95% confidence interval CI, 0.78-1.33), 0.50 (95% CI, 0.37-0.67), and 0.04 (95% CI, 0.02-0.09) events per person-years (PY), respectively. Among patients initially treated with prednisone and cyclophosphamide (n = 44), 91% of patients achieved a remission within 2 years after the initiation of immunosuppressive drug therapy. Characteristics at presentation associated with failing to achieve remission in the univariate analysis were trichiasis (relative risk RR, 0.28; 95% CI, 0.08-097), prior eyelid surgery (RR, 0.11; 95% CI, 0.02-0.78), and esophageal involvement (RR, 0.29; 95% CI, 0.10-0.83). After adjusting for confounding, an initial treatment regimen containing cyclophosphamide and prednisone was associated with a greater likelihood of achieving ocular remission (RR, 8.53; 95% CI, 2.53-28.86; P = 0.001) when compared with other initial treatment regimens. Infections, hematuria, and anemia were the most common side effects observed in patients receiving cyclophosphamide therapy. The rate of discontinuing cyclophosphamide resulting from side effects was 0.20/PY; however, 74% of these patients still achieved remission despite early discontinuation of cyclophosphamide.
In patients with ocular MMP, most achieved ocular disease control with immunosuppressive drug therapy. Treatment with cyclophosphamide and prednisone was strongly associated with the development of ocular remission.
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Paraneoplastic pemphigus
1
is an autoimmune disease that accompanies an overt or occult neoplasm and causes blisters. It is characterized by the presence of IgG autoantibodies that react against ...desmosomal and hemidesmosomal plakin proteins,
2
–
5
desmosomal transmembrane proteins (desmogleins),
6
and an unidentified 170-kd antigen. Blistering of stratified squamous epithelium results from acantholysis, the loss of cell–cell adhesion, induced by pathogenic antibodies against the desmogleins.
6
The most commonly associated neoplasms are, in decreasing order of frequency, non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Castleman's disease, thymoma, retroperitoneal sarcomas, and Waldenström's macroglobulinemia.
Progressive respiratory failure with clinical features of bronchiolitis obliterans is frequently the cause . . .
Mucous membrane pemphigoid and pseudopemphigoid Thorne, Jennifer E; Anhalt, Grant J; Jabs, Douglas A
Ophthalmology (Rochester, Minn.),
2004, 2004-Jan, 2004-1-00, 20040101, Volume:
111, Issue:
1
Journal Article
Peer reviewed
To describe the clinical characteristics of patients with mucous membrane pemphigoid (MMP) and pseudopemphigoid.
Retrospective cohort study.
Two hundred eighty consecutive patients referred for the ...evaluation of possible ocular MMP from January 1, 1985, to December 31, 2001.
Information on patients presenting for evaluation of possible MMP was entered prospectively into a database, which was supplemented by a retrospective chart review. Mucous membrane pemphigoid was diagnosed in patients with a compatible clinical picture by the linear deposition of antibodies to the basement membrane zone (BMZ) on direct immunofluorescent analysis of a mucous membrane biopsy specimen or by the presence of circulating autoantibodies to epithelial BMZ.
Demographic and clinical characteristics of MMP and pseudopemphigoid; risk of ocular MMP among patients presenting with extraocular MMP without ocular disease.
Among patients with ocular MMP, extraocular disease was common (82.4% of patients). The risk of ocular involvement among patients with MMP seen without ocular disease was approximately 5% per year over the first 5 years of follow-up (cumulative risk at 5 years, 22%). Although immunohistologic confirmation of the diagnosis was obtained in all patients, the initial conjunctival biopsy was positive for MMP in 80% of the patients diagnosed with ocular MMP. The most frequent presumed causes of pseudopemphigoid were topical glaucoma medications (28.3%), rosacea blepharoconjunctivitis (20.0%), atopic keratoconjunctivitis (8.3%), and conjunctival lichen planus (8.3%).
Patients with ocular MMP typically have other systemic manifestations of MMP. Patients who are initially seen with extraocular MMP without ocular involvement are at risk for ocular disease developing. The clinical characteristics of ocular MMP and pseudopemphigoid are similar; therefore, immunohistologic evaluation of biopsied tissue is needed to confirm the diagnosis of MMP.
The review included 163 cases of paraneoplastic pemphigus (PNP) reported between 1990 and 2003, including a new unique case of PNP associated with occult breast cancer and an ovarian cyst of ...borderline malignancy.
Hematologic-related neoplasms or disorders were associated with 84% of the cases, with non-Hodgkin lymphoma (38.6%) as the most frequent, followed by chronic lymphocytic leukemia (18.4%) and Castleman's disease (18.4%). The non-hematologic neoplasms comprised 16% of all cases: epithelial origin-carcinoma (8.6%), mesenchymal origin-sarcoma (6.2%), and malignant melanoma (0.6%). Carcinoma cases comprised 58% of the non-hematologic neoplasms. Carcinoma cases (
n=14) consisted of adenocarcinoma (
n=7), squamous cell carcinoma (
n=2), multiple skin tumors probably basal cell carcinoma (
n=1), and bronchogenic carcinoma (
n=1). Of the 10 (6.2%) sarcoma cases, there was one case each of leiomyosarcoma, liposarcoma, malignant nerve sheath tumor, poorly differentiated sarcoma, reticulum cell sarcoma, dendritic cell sarcoma and inflammatory myofibroblastic tumor.
The oral mucosa was involved in all of cases. Isolated oral ulcerations were the first sign in 45% of the cases. Diffuse and persistent oral ulcerations with a progressive course could be a sign of malignancy, either recognized or occult. In the absence of a clear diagnosis, malignancy should be suspected and extensive work-up performed. The full spectrum of signs of PNP may not be present initially. Repeated biopsies, direct and indirect immunofluorescence as well as screening indirect immunofluorescence on murine bladder are required for diagnosis. Clinicians should be highly suspicious when signs and symptoms suggestive of PNP are present in cancer patients, of hematologic and non-hematologic origin.
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