Nonclassical pemphigus with exclusively IgG anti-desmocollin 3-specific antibodies

We describe a patient with nonclassical clinical and histopathological features of pemphigus with exclusively IgG antibodies against desmocollin (Dsc) 3 detected by enzyme-linked immunosorbent assay of recombinant eukaryotic protein of Dsc1-Dsc3. The absence of antibodies against other known targets, such as desmogleins, reinforces the role of anti-Dsc antibodies in the pathophysiology of atypical pemphigus.     

Comparative study of pemphigus vulgaris and pemphigus foliaceus in Singapore

This is a retrospective study of all patients diagnosed to have pemphigus in our centre over a 3 year period. The case records of all patients with pemphigus from January 1995 to December 1997 were analysed. Fifty patients were diagnosed to have pemphigus during the study period. The diagnoses were pemphigus vulgaris in 31 patients, pemphigus foliaceus in 16, paraneoplastic pemphigus in two and IgA pemphigus in one. The average titre of anti-intercellular antibodies in patients with pemphigus vulgaris (1:96) was higher than the titre in patients with pemphigus foliaceus (1:69). The average initial dose of prednisolone required for disease control in patients with pemphigus vulgaris (62 mg/day) was significantly higher than that required for patients with pemphigus foliaceus (44 mg/day). In our study population, pemphigus vulgaris is a more severe and chronic disease than pemphigus foliaceus, as reflected in the higher titre of anti-intercellular antibodies, higher dose of systemic corticosteroids required for control of the disease, the longer duration to achieve complete remission and longer follow-up period.     

Pemphigus vulgaris: a review of treatment over a 19-year period

BACKGROUND: Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes with a high mortality if left untreated. OBJECTIVE: We present a retrospective analysis of 159 patients with pemphigus vulgaris and pemphigus vegetans who were admitted to the Department of Dermatology and Venereology, Zagreb University Hospital Center (Zagreb, Croatia) from 1980 to 1998. RESULTS: Female to male ratio was approximately 2:1. The mean age was 53 years. During the war years in Croatia (1991-95) we noticed a low incidence of pemphigus vulgaris, and from 1996 to 1998 the incidence almost doubled. Diagnosis was based on histopathology [showing typical pemphigus vulgaris changes in 156 (98%) patients], indirect immunofluorescence [positive in 122 (77%) patients], direct immunofluorescence [positive in 141 (89%) patients], and blister smear cytology (Tzanck test) [positive in 115 (72%) patients]. High dosages of prednisone (100-150 mg) were given to 129 patients, which was combined with azathioprine. Patients with refractory pemphigus vulgaris were treated with intramuscular gold (14 patients) and plasmapheresis (five patients). All patients were treated with local ointments. The prolonged use of high doses of corticosteroids and immunosuppressants caused several complications, in particular, steroid diabetes (37 patients), skin infections (26 patients), arterial hypertension (23 patients), cardiorespiratory diseases (22 patients), sepsis (nine patients), etc. During the hospital treatment, 14 patients died, 10 during 1980-89 and only four during the 1990-98 period. The main causes of death were cardiorespiratory failure (six patients) and sepsis (five patients). CONCLUSIONS: Although pemphigus vulgaris is still a life-threatening disease, today it can be successfully treated with a combination of immunosuppressive agents. Early diagnosis and treatment of pemphigus vulgaris allow a better prognosis with lower mortality rates.     

PEMPHIGUS VULGARIS ASSOCIATED WITH SPINDLE CELL THYMOMA

This paper describes the occurrence of fatal pemphigus vulgaris in an 89 year old female, in whom a benign spindle cell thymoma was found at autopsy. The histological appearances of the skin biopsies, thymic tumour and immunofluorescence findings are described. The association between pemphigus and neoplasia is discussed, and the difference between classical pemphigus vulgaris and paraneoplastic pemphigus are evaluated.     

Comparison of desmoglein ELISA and indirect immunofluorescence using two substrates (monkey oesophagus and normal human skin) in the diagnosis of pemphigus

A prospective study was performed to assess the usefulness of desmoglein enzyme-linked immunosorbent assay testing compared with indirect immunofluorescence in the diagnosis of new cases of pemphigus, as well as to compare the relative sensitivities of monkey oesophagus and normal human skin as substrates for indirect immunofluorescence. These tests were performed on the sera of 29 consecutive new cases of pemphigus diagnosed over a 2-year period based on clinical, histological and direct immunofluorescence findings. Desmoglein enzyme-linked immunosorbent assay was positive in all patients whereas indirect immunofluorescence was positive in only 25 of 29 patients. All four patients with negative indirect immunofluorescence had positive antinuclear antibodies or cytoplasmic fluorescence that could have masked the anti-intercellular antibodies. Desmoglein enzyme-linked immunosorbent assay appeared to reflect the disease activity better than indirect immunofluorescence in a few patients who had active disease of recent onset. Monkey oesophagus was found to be superior or equal to human skin as a substrate for indirect immunofluorescence in both pemphigus vulgaris and foliaceus.     

Herpes simplex virus 1 and cytomegalovirus are associated with pemphigus vulgaris but not with pemphigus foliaceus disease

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are blistering autoimmune diseases that depend on interaction between genetic and environmental factors. Viral infections, like herpes simplex viruses 1 and 2 (HSV1/2), cytomegalovirus (CMV), Epstein‐Barr virus and dengue virus, could trigger or exacerbate pemphigus. IgM and IgG antibodies against these viruses in serum from PV and PF, their relatives and controls were determined. HSV1/2 expression was evaluated by direct immunofluorescence (DIF) and qPCR in affected or not oral mucosa from PV patients compared with uninjured PF mucosa. IgG anti‐HSV1 was higher in the PV group compared with all groups. IgG anti‐CMV resulted higher in PV group compared with PF patients and PV relatives. HSV1 was confirmed by DIF and qPCR on oral samples from patients with PV. Lack of HSV1 expression in the oral mucosa of patients with PF corroborate that immunosuppressive therapy cannot be the main cause for HSV1 replication in PV disease.     

A case of pemphigus vulgaris possibly triggered by quinolones

Pemphigus vulgaris is an autoimmune blistering disorder in which both genetic and environmental factors, mainly drugs, are thought to play a part in its aetiopathogenesis. Although some drugs that contain thiol groups, such as D-penicillamine and captopril, and non-thiol drugs, such as cephalosporin, have been reported to trigger or induce pemphigus, there are no previous reports regarding the influence of quinolones in triggering this disease. Here we present a case of pemphigus possibly triggered by quinolones.     

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.     

Pemphigus vegetans with paronychia‐like changes resistant to rituximab therapy

Pemphigus vegetans (PVeg) is a clinical variant of pemphigus vulgaris (PV) that makes up about 2% of all cases. It is distinguished from PV by the presence of vegetative plaques that are usually found in the oral mucosa or intertriginous areas. PVeg can present as one of two clinical subtypes: Hallopeau type and Neumann type. The Hallopeau type is a milder form of the disease, often sparing the oral mucosa. The Neumann type is a more severe form that often includes oral mucosal involvement. Nail unit disease of PVeg is rare, lending to limited recommendations for management. Herein, we present a case of PVeg with paronychia‐like changes following rituximab therapy, along with a brief review of PVeg nail unit disease management. Previously reported treatments include prednisone, azathioprine, dapsone, and cyclosporine. In this patient with nail disease, despite rituximab therapy, intralesional triamcinolone acetonide was effective, thereby avoiding the need for additional immunosuppression.     

Pemphigus vulgaris preceded by herpetiform-like skin lesions with negative immunofluorescence findings

We report a case of pemphigus vulgaris in a 63-year-old woman. At the first onset, she developed herpetiform-like skin lesions. Their histology showed eosinophilic spongiosis and intraepidermal blister formation with an infiltrate of eosinophils. Both direct and indirect immunofluorescence studies were negative. She remained in remission for 6 years. At the second onset, she developed bullous skin lesions; histological examination disclosed suprabasal acantholysis and infiltration of eosinophils. Direct immunofluorescence revealed IgG and C3 deposits at the cell surface, predominantly in the lower epidermis. Indirect immunofluorescence using normal human skin as a substrate demonstrated anti-cell surface IgG antibodies at a titer of 1:160. Immunoblot analysis showed that the patient's serum reacted only with a 130 kD protein. This case indicates that pemphigus vulgaris can follow herpetiform-like skin lesions with negative immunofluorescence findings after a long remission time.     

IgG/IgA pemphigus in a patient with a history of pemphigus vulgaris: An example of epitope spreading?

We report a case of IgG/IgA pemphigus presenting as pemphigus foliaceus following diagnosis and treatment of classic IgG‐mediated pemphigus vulgaris. The dual presentation of IgG and IgA positivity on direct immunofluorescence (DIF) constitutes a rare form of pemphigus with a wide variety of clinicopathologic manifestations. The progression of pemphigus vulgaris is commonly because of epitope spreading. However, the patient's disease was partially refractory to rituximab and showed a change in the DIF with dual staining for IgG and IgA. This indicates that class‐switching may have occurred with epitope spreading or that there was autoreactive IgA at the onset of disease below the threshold of detection by DIF. Our case indicates that in progressive autoimmune disease refractory to treatment, re‐evaluation of the patient for antibody isotypes absent on initial diagnosis may offer key information in better identifying the cause of progression as well as in directing the necessary treatment.     

Minocycline is a useful adjuvant therapy for pemphigus

Pemphigus is an autoimmune blistering disease with high mortality if untreated. The cases of 10 patients who had minocycline 100 mg daily added as adjuvant therapy are reported. Prior to the use of minocycline, all patients had active disease, nine were on prednisolone (10–40 mg) and five were on azathioprine (100–200 mg). The response was assessed on clinical improvement and reduction of immunosuppressive (IS) drugs. It was graded into four categories: major, minor, equivocal and no significant response. A major response was seen in four patients, minor in two, equivocal in one and no improvement in three patients. The prednisolone dose in the six responders was reduced to 0–6 mg (0 mg in three patients), with an average decrease of 21 mg. The average time to respond was 8 months. Of the six responders, three were on azathioprine, which was ceased in two patients and reduced by two-thirds in the other patient. No patient ceased minocycline because of side effects. In conclusion, minocycline 100 mg daily is a simple, safe and well tolerated treatment that should be tried in patients with pemphigus to reduce disease activity and/or the dose of potent IS agents.     

Direct immunofluorescence of the outer root sheath in anagen and telogen hair in pemphigus vulgaris and pemphigus foliaceus

Direct immunofluorescence of peri‐lesional skin is the gold standard in the diagnosis of pemphigus. A specific immunofluorescence pattern may also be demonstrated in the outer root sheath of anagen and telogen hair. We demonstrated an intercellular reticular deposition of immunoglobulin G in the outer root sheath of plucked anagen and telogen hair in all pemphigus vulgaris patients with active disease and for the first time in all patients with active pemphigus foliaceus. Moreover, we demonstrated for the first time that plucked hair samples may be kept at ?20°C for at least 2 weeks before immunofluorescent staining and analysis.     

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.     

天疱疮疗效评估的研究进展

天疱疮作为一种少见却严重的自身免疫性疾病,以皮肤黏膜损害为主要特征,因此对其的疗效评估在皮肤科领域尤为重要,尤其是在对于使用激素及免疫抑制剂的选择方面。目前,国内相关天疱疮的临床试验应用评估标准较为欠缺,这将导致无法进行结果可靠性的判断,同类研究的试验结果间也无法比较。因此,本文将对天疱疮的疗效评估进展做一综述。     

以龟头包皮黏膜皮损为首发的天疱疮一例

患者男,54岁。因龟头包皮发生皮疹、破溃伴瘙痒半年,胸部发疹1.5个月于2011年12月12日就诊。患者半年前,无明显诱因包皮龟头处出现米粒大小皮疹,伴有瘙痒及疼痛,就诊于当地医院,诊断为龟头包皮炎,给予阿奇霉素、左氧氟沙星治疗1周,皮损未见好转。以后皮损逐渐变大,局部破溃、糜烂、渗出,继续按包皮龟头炎治疗,给予呋喃西林外用,皮损时轻时重,但始终未愈……     

副肿瘤性天疱疮二例

副肿瘤性天疱疮是一种自身免疫性大疱性疾病,临床表现为严重疼痛性粘膜糜烂和多形性皮损,组织病理学显示棘层松解、苔藓样皮炎或角质形成细胞坏死,存在对各种上皮蛋白的自身抗体,同时伴随潜在肿瘤。本文首次报道 2例临床、组织学和免疫病理学均符合副肿瘤性天疱疮病例,伴随 Castleman肿瘤。     

副肿瘤性天疱疮1例

报告1例副肿瘤性天疱疮,男性,21岁。临床特点:严重疼痛性粘膜糜烂和多形性皮损。组织病理学显示棘层松解、苔藓样皮炎或角质形成细胞坏死。B超和CT示下腹部偏右侧有一11.2cm×7.6cm×8.4cm包块。术后病理证实为非何杰金淋巴瘤。     

Paraneoplastic pemphigus secondary to fludarabine evolving into unusual oral pemphigus vegetans

We report a patient with chronic lymphocytic leukaemia who developed paraneoplastic pemphigus (PNP) soon after the initiation of fludarabine therapy. He presented with severe oral and cutaneous erosions. Initially, he had high titres of circulating autoantibodies as detected by indirect immunofluorescence (IF) on multiple epithelial substrates (normal human skin, monkey oesophagus, and rat bladder) and by desmoglein 1 and 3 enzyme-linked immunosorbent assays (ELISAs). His oral erosions have subsequently progressed into unusual hyperplastic papillomatous lesions affecting the inner aspect of lips and buccal mucosae, histologically consistent with pemphigus vegetans. Desmoglein 1 antibodies and IF on rat bladder substrate have become negative after 18 months of therapy. Several agents had been initiated to bring the disease under control originally, but a partial remission was achieved and maintained with mycophenolate mofetil and low-dose prednisolone.