The treatment of mild pemphigus vulgaris and pemphigus foliaceus with a topical corticosteroid

Seven patients with mild pemphigus vulgaris (n = 3) or pemphigus foliaceus (n = 4) were treated with a very potent topical corticosteroid alone. Clobetasol propionate 0.05% cream was applied to mucosal lesions and involved skin twice a day for at least 15 days, then progressively tapered. Pemphigus was considered to be controlled if healing of lesions was obtained, with a 75% decrease in the number of new lesions per week without addition of any systemic treatment. In all seven patients, the disease was controlled initially with healing of cutaneous lesions within 15 days, while healing of mucosal lesions took at least 1 month. In four patients, remission was maintained with topical corticosteroid alone for a mean 19-month follow-up. In three patients, relapse occurred after 2-11 months, requiring a systemic treatment.     

Rituximab in autoimmune bullous diseases: mixed responses and adverse effects

BACKGROUND: Intolerably high doses of systemic corticosteroids and additional immunosuppressants may be required to control disease activity in autoimmune bullous skin diseases. New therapeutic options are needed for such patients. OBJECTIVES: To determine the efficacy and adverse effects of adjuvant rituximab. METHODS: Seven patients with refractory autoimmune blistering diseases (pemphigus vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid, MMP, n = 1) were treated four times with rituximab at an individual dose of 375 mg m(-2) at weekly intervals. RESULTS: All lesions cleared in three patients (two PV, one BP), while they were reduced by more than 50% in three others (two PV, one BP). The concomitant immunosuppressive medication was reduced in five patients (four PV, one BP). The patient with MMP developed bilateral blindness while nasopharyngeal lesions resolved. Three patients (two BP, one PV) experienced severe adverse events including fatal pneumonia. CONCLUSIONS: Adjuvant B-cell depletion by rituximab is effective in otherwise therapy-resistant bullous autoimmune disorders but may be associated with substantial adverse effects including fatal outcomes.     

Topical epidermal growth factor for the improvement of acne lesions: a randomized,double‐blinded,placebo‐controlled,split‐face trial

Acne is one of the most common adverse events associated with the use of anticancer agents, such as epidermal growth factor receptor (EGFR) inhibitors. Based on data from several previous reports, we predicted that topical application of EGF could improve acne vulgaris. To evaluate the clinical efficacy and safety of topical recombinant human EGF (rhEGF) cream for the treatment of facial acne vulgaris. Twenty Korean adults with mild to moderate acne vulgaris applied topical rhEGF cream on one half of the face and a vehicle cream on the other half twice daily for six weeks. Clinical assessments were conducted at baseline, two, four, and six weeks. Two assessment methods were applied: inflammatory and non‐inflammatory acne lesion counts and acne severity score by investigator's global assessment. Skin sebum output level and hydration level were also measured at each visit. All volunteers completed the study. At the final visit, inflammatory acne lesions were reduced by 33.5% on the rhEGF‐applied side. Non‐inflammatory acne lesions also decreased by 25.4%, whereas the lesions on the control side increased. The majority of patients demonstrated improvement on the side of the face where rhEGF cream was applied. Sebum output decreased on the rhEGF side, and skin hydration level increased on both sides. No severe side effects were observed during the study. Topical rhEGF seems to be an effective and safe adjuvant treatment option for mild to moderate acne vulgaris.     

Wound healing after laser skin resurfacing: The effect of a silver sulfadiazine-hyaluronic acid-containing cream under an occlusive dressing

Abstract

Introduction: Occlusive dressings promote wound healing after laser skin resurfacing. Our goal was to evaluate whether a cream containing hyaluronic acid–silver sulfadiazine could improve this process. Methods: Ten guinea pigs received laser resurfacing on the skin of their backs. Polyurethane foam film adhesive dressing was applied. A cream containing hyaluronic acid–silver sulfadiazine was applied under the dressing over half of the wound. Skin biopsies were taken at days 2, 4, 7 and 9 and examined by a pathologist blinded to the study. Results: Re-epithelialization appeared to occur faster in the cream-treated areas, together with a lower level of acute inflammation in the early phase of the healing process. Conclusions: The cream containing silver sulfadiazine/hyaluronic acid seems to improve wound healing after laser skin resurfacing in guinea pigs. The clinical application of this finding on humans should be assessed.     

Deposition of the membrane attack complex of complement in pemphigus vulgaris and pemphigus foliaceus skin

The present study was performed to determine whether complement activation in pemphigus vulgaris (PV) and pemphigus foliaceus (PF) results in the assembly of the terminal complement sequence or membrane attack complex (MAC) in skin lesions. Biopsy specimens of skin lesions from five patients with PV and three patients with PF contained C5, C7, C9, and the MAC related neoantigen (C5b-9 neoantigen) in intercellular substance areas (ICS), as well as IgG and the early complement components Clq, C4, and C3. The presence of these late complement components and the C5b-9 neoantigens in ICS sites of the skin lesions is indicative of complement activation by the pemphigus antibody, with subsequent assembly of the MAC. The binding of IgG and early complement components to ICS was observed in both non-lesional (normal appearing) skin and in skin lesions. However, no MAC could be detected in the normal appearing skin of our pemphigus patients. It was also noted that the MAC could be generated in vitro on cryostat sectioned normal human skin by pemphigus antibody in the presence of complement. Results of these studies suggest that complement activation may be related to membrane damage of epidermal cells in both PV and PF.     

Cutaneous type pemphigus vulgaris: a rare clinical phenotype of pemphigus

Pemphigus is an autoimmune blistering disease of the skin, mucous membranes, or both. There are two main categories of pemphigus: pemphigus foliaceus (PF) and pemphigus vulgaris (PV). PV is further subdivided into mucosal dominant and mucocutaneous types, according to the extent of cutaneous lesions. These classes of pemphigus have distinct histopathologic and serologic findings, with most cases falling into these subtypes. We report 4 cases that clinically showed blisters and erosions in the skin only, without mucosal involvement. Histologic examination of cutaneous lesions demonstrated suprabasilar acantholysis, a typical finding for PV. These patients had predominant anti-desmoglein 1 (Dsg1) IgG autoantibodies as well as anti-Dsg3 IgG autoantibodies, as determined by enzyme-linked immunosorbent assay. The desmoglein compensation theory posits that this rare phenotype can be produced by pathogenically weak anti-Dsg3 IgG in the presence of potent anti-Dsg1 IgG autoantibodies. Thus, cutaneous type PV without apparent mucosal involvement is observed as a rare clinical and histologic expression of pemphigus. This expression can be a transient phenotype that may develop from, or evolve into, other subtypes of pemphigus.     

Regional variation in the expression of pemphigus foliaceus, pemphigus erythematosus, and pemphigus vulgaris antigens in human skin

The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies. Regional variations were observed in the expression of all these antigens. The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp. This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp. These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus.     

Epidemiologic analysis and clinical course of 84 consecutive cases of pemphigus in eastern Sicily

Background The purpose of this study was to examine the clinical and epidemiologic features of pemphigus in eastern Sicily.
Methods All new cases of pemphigus seen in the Dermatology Clinic at the University of Catania during the period January 1982 to June 1996 were studied retrospectively.
Results Eighty-four patients with pemphigus represented 1.3% of 6653 patients admitted to our clinic in a 13.5-year period, with an average annual incidence of six cases per year. The most common form of presentation was pemphigus vulgaris (PV) (75%), followed by pemphigus erythematosus (17%), pemphigus herpetiformis (6%), and pemphigus vegetans (2%). In 6% of PV patients, the oral lesions were not followed by skin involvement, and the lag time between the onset of illness and the final diagnosis in five PV cases was prolonged, ranging from 4 to 7 years, probably due to the mild clinical presentation of the disease. Two trauma-related PV cases were documented; in one case, the blisters were located in a surgical scar and in the other in a burn scar.
Conclusions Our findings showed that pemphigus has a relatively high prevalence in eastern Sicily compared with other Italian regions; PV is the most common variant, and may have a mild course not always requiring aggressive therapy.     

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)     

Healing effect of Pilocarpine gel 4% on skin lesions of pemphigus vulgaris

BACKGROUND: The high rate of morbidity and mortality resulting from long-term use of corticosteroids in pemphigus vulgaris (PV) warrants discovery of a new treatment strategy. Based on a new theory on the pathophysiology of PV, cholinomimetics can block the process of blister formation. AIMS: This study was conducted to evaluate the clinical effectiveness of Pilocarpine gel in the treatment of skin lesions of PV. METHODS: In a double-blind, placebo-controlled study, three PV patients with a total of 64 skin lesions were treated by either Pilocarpine or placebo gel. After 15 days of treatment an epithelialization index of the two groups was compared. RESULTS: The mean of the epithelialization index in skin lesions that received Pilocarpine was significantly higher than that of the placebo group (40.3 +/- 1.7 vs. 24.4 +/- 3.3, P < 0.001). CONCLUSIONS: Pilocarpine gel effectively treats PV.     

Ear,nose and throat involvement in patients with pemphigus vulgaris: correlation with severity,phenotype and disease activity

Background Pemphigus vulgaris (PV) is the most common clinical form of pemphigus that is characterized by easily ruptured or loose bulla formation on skin and/or mucosa. The frequency of the ear, nose and throat involvement of PV is not clearly defined. Objectives To evaluate the frequency of ear, nose and throat (ENT) involvement in patients suffering from PV who had been recently diagnosed or exacerbated under follow up and to determine the association with ENT symptoms, clinical involvement, severity and duration of pemphigus vulgaris. Materials and Methods The study group included a total of 38 PV patients comprising 24 new patients and 14 patients who showed exacerbations while on complete remission or under treatment. All patients were asked about ENT symptoms and endoscopic examination were performed to evaluate the presence of nasal, pharynx, larynx and ear involvement. Results Of the 38 patients, 33 (87%) had active PV lesions on endoscopic evaluation. Twenty‐five patients (66%) had lesions on pharynx, twenty‐one (55%) on larynx, twenty‐nine (76%) on nasal mucosa and four (10%) on the ear mucosa. ENT involvement was not associated with the severity and the clinical involvement of the disease. Pharyngeal and nasal involvement was significantly associated with symptoms, while laryngeal and ear involvement was not found to be significantly associated with symptoms. Nasal and ear involvement was not associated with the duration of the disease while pharyngeal and laryngeal involvement favored newly diagnosed patients. Conclusions Our results revealed that high number of patients with PV may present with active ENT lesions, furthermore patients with ear, nose and throat involvement may be asymptomatic and active lesions may be found in patients without any ENT symptoms. Therefore it should be considered that to understand the real extent of PV involvement, endoscopic ENT evaluation should be performed in patients with or without symptoms.     

Persistent vegetating and keratotic lesions in patients with pemphigus vulgaris during immunosuppressive therapy

We describe three patients with pemphigus vulgaris, who during treatment with low doses of immunosuppressive drugs developed persistent keratotic or vegetating skin lesions. Direct immunofluorescence (IF) examination of these lesions showed the typical findings of pemphigus.     

Neonatal Pemphigus Vulgaris: Trsmtel Transmission of Antibodies

A male infant with skin lesions was born to a 28-year-old mother who was under treatment for pemphigus vulgaris (PV), diagnosed eight years earlier. Circulating IgG class pemphigus antibody was found in the infant's blood, and deposition of IgG in the intercellular spaces of the epidermis was seen. The infant's lesions resolved within three weeks, and pemphigus antibody titer became negative by seven weeks. The pathogenetic role of PV antibodies and the risk for a fetus of a mother suffering from PV are discussed.     

Silk sericin ameliorates wound healing and its clinical efficacy in burn wounds

The aim of this study was to evaluate the effect of silk sericin, a protein from silkworm cocoon, on scratch wound healing in vitro. For applicable result in clinical use, we also study the efficacy of sericin added to a standard antimicrobial cream, silver zinc sulfadiazine, for open wound care in the treatment of second-degree burn wounds. In vitro scratch assays show that sericin at concentration 100 μg/mL can promote the migration of fibroblast L929 cells similar to epidermal growth factor (positive control) at 100 μg/mL. After 1 day of treatment, the length of scratch in wounds treated with sericin was significantly shorter than the length of negative control wounds (culture medium without sericin). For clinical study, a total of 29 patients with 65 burn wounds which covered no less than 15 % of total body surface area were randomly assigned to either control (wounds treated with silver zinc sulfadiazine cream) or treatment (wounds treated with silver zinc sulfadiazine with added sericin cream) group in this randomized, double-blind, standard-controlled study. The results showed that the average time to reach 70 % re-epithelialization of the burned surface and complete healing in the treatment group was significantly shorter, approximately 5–7 days, than in the control group. Regarding time for complete healing, control wounds took approximately 29.28 ± 9.27 days, while wounds treated with silver zinc sulfadiazine with added sericin cream took approximately 22.42 ± 6.33 days, (p = 0.001). No infection or severe reaction was found in any wounds. This is the first clinical study to show that silk sericin is safe and beneficial for burn wound treatment when it is added to silver sulfadiazine cream.     

Mucocutaneous pemphigus vulgaris carrying high-titre antidesmoglein 1 antibodies with skin lesions resembling pemphigus erythematosus

Patients with pemphigus vulgaris (PV) who have both antidesmoglein (Dsg)1 and anti-Dsg3 antibodies usually develop flaccid blisters on skin and mucous membranes. We report a case of PV with crusting skin lesions resembling pemphigus erythematosus, the localized variant of pemphigus foliaceus (PF). Notably, the patient had high titres of anti-Dsg1 IgG, as assessed by ELISA. We then established an in vitro model of pemphigus, and found that patient's serum was able to induce suprabasilar acantholysis in mouse skin culture. However, epidermal splitting also occurred within the granular layer, suggesting that the pathogenic potential of such a high-titre anti-Dsg1 serum was intermediate between PV and PF. Thus, the levels of anti-Dsg1 antibodies could play a role in determining the clinical phenotype of pemphigus.     

Sensitivity to ampicillin in pemphigus vulgaris patients and first-degree healthy relatives

Objective To elucidate the relationship between the endogenous and exogenous factors involved in pemphigus vulgaris. Background Based on the observation that patients suffering hypersensitivity to penicillin often develop intercellular antibodies indistinguishable from those typical of pemphigus, it was decided to examine the hypersensitivity to a widely used semi-synthetic penicillin, ampicillin, in pemphigus vulgaris (PV) patients and their blood relatives. Methods Hypersensitivity was tested by macrophage migration inhibition factor (MIF) and mast cell degranulation (MCD) tests in 13 pemphigus vulgaris (PV) patients and 24 of their first-degree relatives. Results The humoral immune response to ampicillin was increased in PV patients and their relatives compared to controls. The cell mediated immune response was increased in the relatives compared to the controls, and negative in all patients, probably due to steroid therapy. Conclusions Increased humoral hypersensitivity to ampicillin in both PV patients and their relatives emphasizes the close relationship between drugs and the pathogenesis of the disease, and points to a possible genetic predisposition.     

Efficacy of perilesional and intralesional triamcinolone acetonide injections in pemphigus vulgaris lesions of the scalp: an effective therapeutic option

The scalp is a common location for pemphigus vulgaris (PV), and scalp lesions may be resistant to standard treatment. Perilesional/intralesional triamcinolone acetonide (TA) injections have been used successfully to treat oropharyngeal and ocular involvement in PV. Data on the efficacy of perilesional and intralesional triamcinolone acetonide injections in scalp lesions in PV are lacking. We report two patients with immunopathologically and histopathologically confirmed PV and residual scalp lesions resistant to standard treatment, who were treated with perilesional and intralesional injections of TA 10 mg/mL. Clearance of scalp lesions was achieved after one after, respectively, one and two perilesional and intralesional injections. Perilesional and intralesional TA injections may serve as an effective and safe treatment for recalcitrant scalp lesions in pemphigus.     

Study of desmoglein 1 and 3 antibody levels in relation to disease severity in Indian patients with pemphigus

OBJECTIVES: To conduct a cross-sectional study to compare Dsg1 and Dsg3 antibody levels independently with severity of disease activity in pemphigus vulgaris (PV) and pemphigus foliaceus (PF). METHODS: Blood samples from 44 patients with pemphigus (PV-38, PF-6) were analyzed using ELISA. The severity of skin and mucosal disease was graded using a score from 0 to 3. RESULTS: A statistically significant correlation between increase in Dsg 3 antibody titres with severity of oral involvement and Dsg 1 titres with severity of skin involvement was found in both PV and PF patients (p < 0.01). However, we were unable to demonstrate a relationship between increased titres of Dsg1 and Dsg 3 antibodies with oral and skin involvement respectively. CONCLUSION: This study suggests that the severity of skin and oral disease in pemphigus is determined by the quantities of Dsg1 and Dsg3 antibodies respectively.     

Clinical and immunological profile of umbilical involvement in pemphigus vulgaris and pemphigus foliaceus

Background. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune vesicobullous disorders with IgG autoantibodies directed against desmoglein (Dsg)1 and 3, which lead to intraepidermal acantholysis. Aim. To characterize the clinical and immunological profile of patients with PF or PV with umbilical involvement. Methods. In total, 10 patients (7 women, 3 men; age range 24–70 years, disease duration 3–16 years) diagnosed with either PV (n = 5) or mucocutaneous PF (n = 5) were assessed according to their clinical features, histopathology and immunological findings [direct and indirect immunofluorescence (DIF and IIF) and ELISA with recombinant Dsg1 and Dsg3]. Results. Erythema, erosions, crusts and vegetating skin lesions were the main clinical features of the umbilical region. DIF of the umbilical region gave positive results for intercellular epidermal IgG and C3 deposits in eight patients and for IgG alone in the other two. Indirect immunofluorescence with IgG conjugate showing the typical pemphigus pattern was positive in all 10 patients, with titres varying from 1 : 160 to 1 : 2560. ELISA with recombinant Dsg1 gave scores of 24–266 in PF and 0–270 in PV. Reactivity to recombinant Dsg3 was positive in all five patients with PV (ELISA 22–98) and was negative in all PF sera. Conclusions. All 10 patients with pemphigus with umbilical presentation had the clinical and immunopathological features of either PF or PV. This peculiar presentation, not yet completely elucidated, has rarely been reported in the literature. A possible explanation for this unique presentation may be the presence of either novel epitopes or an association with embryonic or scar tissue located in the umbilical‐cord region.     

A comparison of anti-desmoglein antibodies and indirect immunofluorescence in the serodiagnosis of pemphigus vulgaris

BACKGROUND: Indirect immunofluorescence (IIF) is the standard method for the detection of pemphigus autoantibodies. Commercially available enzyme-linked immunosorbent assays (ELISAs) have recently become available to measure serum antibodies (Abs) against desmoglein1 (Dsg1) and desmoglein3 (Dsg3). It has been suggested that patients with mucosal-dominant pemphigus vulgaris (PV) have serum Abs against Dsg3 only, patients with mucocutaneous PV have Abs to both Dsg1 and Dsg3, and patients with pemphigus foliaceus (PF) have Abs against Dsg1 only. AIM: To compare the sensitivity and specificity of the IIF and ELISA tests in the diagnosis of pemphigus and its subsets. METHODS: Thirty-three patients with PV and five patients with PF were studied, and compared with 50 healthy individuals or patients with unrelated skin diseases. Monkey esophagus was used as a substrate for the IIF test. RESULTS: The IIF and ELISA tests were each positive in 26 of the 32 (81%) PV patients, and in none (0%) and 3 (6%) of the 50 controls, respectively. Both the IIF and ELISA results were concordant in 69% of the PV patients, and only one of these two tests was positive in the remaining 31% of patients. Forty-six per cent of the PV patients with a positive ELISA test did not have the PV phenotype (mucosal or mucocutaneous) predicted by their autoantibody profile. CONCLUSION: The IIF and ELISA tests may be used as complementary tests for the serologic diagnosis of pemphigus.