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.     

Castleman's disease associated pemphigus. A form of paraneoplastic pemphigus

We report a patient with Castleman's disease (angio-follicular lymph node hyperplasia) associated with a pemphigus vulgaris-Iike disorder. The patient had the hyaline-vascular mediastinal type of Castleman's disease and developed painful oral erosions and penile lesions.
Histologic examination revealed an interface dermatitis including vacuolar changes, necrotic keratinocytes and a lichenoid infiltrate. In addition there was suprabasal vesiculation with acantholysis, reminiscent of pemphigus vulgaris. Direct immunoperoxidase staining for intercellular igG was positive.
HLA typing revealed that the patient did not have an HLA haplotype known to he associated with susceptibility to pemphigus.
Until now, Castleman's disease Associated Pemphigus (CDAP) has been regarded as a unique entity presenting as atypical pemphigus vulgaris. However, a review of the literature reveals that the clinical and histologic signs of CDAP are virtually identical to those of paraneoplastic pemphigus and that both entities are associated with a lymphoproiiferative disorder. We suggest that CDAP is a form of paraneoplastie pemphigus.     

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.     

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.     

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.     

Case of pemphigus foliaceus that shifted into pemphigus vulgaris after adrenal tumor resection

A 79-year-old Japanese woman visited our hospital on 6 May 2003, who had suffered from erythema and crusted vesicles located on the head, face and trunk. The eruptions first appeared in February 2003. Histopathological findings included blister formation spreading from just below the horny layers to the upper squamous layers, where acantholytic cells were observed. Direct immunofluorescence disclosed immunoglobulin G depositions in the epidermal intercellular spaces. Enzyme-linked immunosorbent assay showed an elevated titer of anti-desmoglein (Dsg)1 autoantibodies (154 index value), but almost normal levels of anti-Dsg3 autoantibodies (8 index value in serum). The diagnosis at first was made as pemphigus foliaceus (PF). Topical use of corticosteroids alone could control the eruptions well. Systemic examinations on admission revealed a right adrenal tumor that had caused Cushing's syndrome. Its resection was performed on 24 July 2003. Histopathological diagnosis of the removed tumor was a functional adrenal adenoma. The symptoms had worsened after the resection. Topical use of corticosteroids alone could no longer control the symptoms. Additional p.o. medications of minocycline hydrochloride and nicotinic acid amides improved the symptoms to some extent. However, oral cavity erosions appeared in December 2004, and the titer of anti-Dsg3 autoantibodies in serum elevated, suggesting a transition from PF to pemphigus vulgaris (PV). p.o. administration of corticosteroids started, which improved the symptoms significantly. To date, there have been no reports of pemphigus complicated with an adrenal tumor that caused Cushing's syndrome in Japan. The present case is particularly interesting in that the symptoms became worse after the tumor resection and that the first diagnosis of PF shifted into PV after the operation.     

The transition of pemphigus vulgaris into pemphigus foliaceus: a reflection of changing desmoglein 1 and 3 autoantibody levels in pemphigus vulgaris

The transition of pemphigus vulgaris (PV) into pemphigus foliaceus (PF) is rare and the immunological changes underlying this event are not well understood. We report a 44-year-old woman who presented with oral and cutaneous erosions typical of PV. Over a 9-year period, the clinical features evolved into those of PF. To examine whether quantitative changes in desmoglein (Dsg) antibodies were associated with this transition, Dsg1 and Dsg3 antibody levels were measured by enzyme-linked immunosorbent assay in 82 sequential serum samples collected over this period. At presentation, when the phenotype was PV with oral and cutaneous erosions, antibodies to both Dsg1 and Dsg3 were detected. The disappearance of oral involvement was associated with a decline in Dsg3 antibodies, which are now undetectable, while the development of more severe skin involvement was associated with rising Dsg1 antibody levels. These data strongly suggest that the change in clinical features is a reflection of qualitative and quantitative changes in antibody profile. It is not known whether the transition to PF is permanent or whether disease relapses in the future may be associated with the re-emergence of Dsg3 antibodies, oral ulceration and a PV phenotype.     

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。     

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.     

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.     

天疱疮合并症的研究进展

天疱疮是一种以表皮内棘层松解为特征的自身免疫性大疱性皮肤病。天疱疮可以合并银屑病、神经系统疾病、血液系统疾病、其他自身免疫性疾病以及肿瘤等。近年来有关天疱疮合并症的报道越来越多,本文对天疱疮合并症的研究进展作一综述。     

Dexamethasone pulse therapy in pemphigus

Pulse therapy with high-dose glucocorticoids was introduced 20 years ago as a treatment modality for autoimmune disease and transplant rejection. The most popular dermatological indication for pulse therapy is severe pemphigus. We reviewed the sequelae of 14 patients with pemphigus who were treated by pulse therapy. Seven of them reached complete remission, although three of them needed a new pulse course due to disease flare-up. Adverse events were minor and confined to 60% of all patients: temporary facial flushing during pulse administration, sleep disturbances during the first night after pulse administration, and mood changes occurred during the week of pulse therapy. The study showed the possibility of oral instead of an intravenous mute of dexamethasone pulse administration, which makes double-blind placebo-controlled trials ethically feasible. Fifty per cent of the patients reached complete remission. This retrospective study does not allow claims on the steroid-sparing effect.     

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.     

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.     

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。     

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.     

Paraneoplastic pemphigus presenting as erythrodermic lichenoid dermatitis with concomitant features of pemphigus foliaceus

We describe a patient with paraneoplastic pemphigus who presented with erythrodermic lichenoid dermatitis, later developing blisters of pemphigus foliaceus type and oral erosive lesions. In addition to antibodies against the plakin family proteins, the patient's serum was positive for anti-desmoglein 1 antibodies without coexisting anti-desmoglein 3 activities by enzyme-linked immunosorbent assay, which is a very rare autoantibody profile in paraneoplastic pemphigus.     

A mild form of captopril-induced pemphigus

We describe a mild form of drug-induced pemphigus in a woman with essential arterial hypertension treated with captopril. Complete recovery was observed three weeks after the therapy had been discontinued.     

口服阿莫西林后发生天疱疮

报告1例口服阿莫西林后发生天疱疮的病例。患者男,40岁。因全身出现红斑、水疱1个月后就诊。1个月前患者全身皮肤出现散在黄豆大红斑、瘙痒,2d后在红斑和正常皮肤上出现水疱,水疱破裂后干燥结痂,但仍有新发水疱,皮损多分布在胸、背、颈部和腋下。经口服泼尼松20mg/d治疗2周后,皮损基本消退,5d前全身又出现红斑和水疱,皮损瘙痒。患者2次发病前均有口服阿莫西林史。皮肤科检查:躯干和四肢可见大小不一的散在水肿性红斑,部分红斑上可见松弛性水疱,尼氏征阳性,皮损组织病理检查示表皮内水疱和棘刺松解细胞,免疫组化组织病理示在表皮内IgG、C3呈网状沉积。体外γ干扰素释放实验阳性。最终诊断为药物诱发的天疱疮。     

Involvement of UV-irradiation in pemphigus foliaceus

Ultraviolet (UV) light has been implicated in inducing acantholysis in the uninvolved skin of pemphigus patients. This report presents the case of a 55-year-old man with pemphigus foliaceus in whom skin lesions were induced and exacerbated by UV-irradiation.