A case of pemphigus vulgaris in a six-year-old girl

A case of pemphigus vulgaris in a six-year-old Japanese girl is presented. She first developed vesicles and ulcerations in oral and laryngeal mucous membranes, showing a hoarse voice and fits of coughing with excessive slavering. She had skin blisters six months later. Biopsy of the skin lesion demonstrated the intraepidermal blister in a suprabasal location. Direct immunofluorescence (IF) of the skin lesion revealed deposits of IgG and C3. Indirect IF showed serum anti-ICS antibody titer at 1:640. She was diagnosed as having pemphigus vulgaris. Treatment with oral prednisolone (1 mg/kg) proved effective. This is the first case of infantile pemphigus vulgaris in Japan.     

系统性红斑狼疮并发寻常型天疱疮

报告1例系统性红斑狼疮并发寻常型天疱疮.患者女,42岁.面部出现红色斑丘疹伴四肢关节疼痛4年,同时出现光敏、血液系统异常,血清抗核抗体、抗ds-DNA抗体均阳性.2年前口腔黏膜反复出现糜烂,后躯干、四肢出现水疱,水疱破溃后形成不易愈合的糜烂面,经皮损组织病理检查、免疫荧光检查,诊断为寻常型天疱疮.     

Nail involvement in pemphigus vulgaris

BACKGROUND: Involvement of the nail unit in pemphigus vulgaris (PV) is thought to be rare. OBJECTIVES: To determine the frequency of nail changes among patients with PV. METHODS: Nail changes were recorded in patients with PV and were analysed retrospectively. Biopsies were taken from the nail bed and nail matrix for histological and immunofluorescence observations. Microscopic (potassium hydroxide) examination and fungal culture were performed. RESULTS: Nail changes were present in 30 of 64 (47%) patients with PV. Sixteen patients had onychomycosis and 14 had nail changes due to PV. These included onychomadesis, discoloration, deformity, onychorrhexis, onycholysis, subungual haemorrhage, subungual hyperkeratosis and paronychia. Onychomycosis affected fingernails and toenails, but changes due to PV occurred only in fingernails, most commonly on the thumb and index finger. No connection was found between the patient's occupation and nail involvement, and there was no correlation with the severity or duration of PV. In a control group of 64 patients of similar sex and age, only two had non-specific fingernail changes. CONCLUSIONS: Nail changes in PV may be more frequent than previously thought.     

Childhood pemphigus vulgaris: five cases in 16 years

Pemphigus vulgaris (PV) usually occurs in adults. There are only a few reports of large PV series concerning childhood cases. We report here five cases of PV in patients younger than 16 years. They were analyzed among 169 PV cases out of a total of 192 pemphigus patients diagnosed between 1988-2004. The ratio of childhood cases was 2.9% in our large PV series. This relatively high ratio of childhood patients suggests that PV should not be neglected in the differential diagnosis of bullous lesions in childhood. Four of the five cases were followed up between 2-4 years and all of these four cases showed at least one relapse. PV also seems to show a relapsing course in the pediatric age group like in adults.     

Outcome of pemphigus vulgaris

Background Pemphigus vulgaris can be divided into mucosal, mucocutaneous and cutaneous subtypes. A higher mortality rate has been shown with mucocutaneous involvement. Objectives The aim of this retrospective study was to analyse the association of clinical subtypes of pemphigus vulgaris with remission rates. Patients/methods One hundred twenty‐eight patients with pemphigus vulgaris, treated with prednisolone 2 mg/kg/day plus azathioprine 2 to 2.5 mg/kg/day, were enrolled. The partial and complete remission rates, at the end of the first and second years of treatment, and the number of relapses were compared in the three groups. Results After disease establishment, 71.1% had mucocutaneous, 18.8% had mucosal, and 10.2% had only cutaneous involvement. The mean duration of follow‐up was 53.5 ± 39.6 months. The mean duration it took the mucocutaneous group to reach a prednisolone dosage of 30 mg/day was significantly longer (P = 0.050). Mucocutaneous patients had a significantly lower rate of remission (31.9%) compared with those with only mucosal or cutaneous involvement (48.6%) at the end of the first year of the treatment (P = 0.029). After 2 years, mucocutaneous patients again had a lower remission rate (32.9% vs. 44.5%). Relapses were also more frequent in this subtype. Those presenting with mucosal or mucocutaneous erosions had a higher rate of active disease after receiving treatment for a year compared with those with only cutaneous presentation (66.7% vs. 45%; P = 0.057). Conclusions In mucocutaneous subtype, clinical control was achieved later, and they had a lower rate of remission at the end of the first and second years of treatment. They were also prone to relapses.     

Successful treatment of adolescent pemphigus vulgaris by immunoadsorption method.

A 15-year-old girl with pemphigus vulgaris did not respond to oral administration of prednisolone at 45 mg/day. The skin and oral mucous membrane lesions recurred after effective treatments with methylprednisolone pulse therapy and combination therapy with prednisolone and cyclosporine. The finally successful treatment involved eleven cycles of immunoadsorption using a tryptophan column and administration of a moderate dose of prednisolone. Serum gamma-globulin level and anti-intercellular antibody titer decreased from 1.08 g/dl to 0.5 g/dl and 1:320 to 1:20, respectively. She has been well controlled with 21.5 mg/day prednisolone for 8 months after the final adsorption. Considering the physical, mental and social situation of adolescent student patients, immunoadsorption is a highly preferable choice among a variety of treatment modalities for pemphigus vulgaris because it makes the term of hospitalization shorter and avoids undesirable side effects from initial high dose corticosteroids.     

Signalling pathways in pemphigus vulgaris

Acantholysis in pemphigus vulgaris is induced by binding of autoantibodies to desmoglein 3 (Dsg3). The roles of signalling pathways on development of acantholysis have recently been extensively studied. In the study by Sayar et al., recently published in Exp Dermatol, epidermal growth factor receptor (EGFR) signalling was activated in both in vivo and in vitro pemphigus vulgaris experimental models. However, while EGFR inhibitors suppressed activity of p38 mitogen‐activated protein kinase (p38MAPK) linearly, they suppressed activity of c‐Myc and acantholysis in a non‐linear, V‐shaped relationship. These findings indicated complicated interactions among EGFR, p38MAPK and c‐Myc in pemphigus vulgaris pathology.     

Rituximab in refractory pemphigus vulgaris

ABSTRACT:  Pemphigus vulgaris (PV) is a severe chronic autoimmune blistering disease of skin and mucous membranes. The use of systemic corticosteroids in pemphigus has dramatically reduced its mortality rate, but the long-term use of steroids leads to severe side effects, many of which are serious. For this reason it is often necessary to add immunosuppressive agents to the regimen. However, there are occasional refractory cases in which therapy with conventionally accepted modalities is either not efficacious or not possible on account of side effects. Rituximab is a therapeutic monoclonal antibody targeting CD20, an integral membrane protein highly expressed on the surface of pre-B lymphocytes and activated mature B lymphocytes. We present an instance of refractory PV successfully treated with rituximab. The successful treatment of pemphigus described here demonstrates that rituximab is a viable therapeutic option for patients with refractory PV.     

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.     

Antidesmoplakin antibodies in pemphigus vulgaris

Background Besides being present in paraneoplastic pemphigus (PNP), circulating antidesmoplakin (DP) antibodies have been found anecdotally in other bullous diseases, including pemphigus foliaceus and pemphigus vulgaris. Objectives To verify how frequent anti‐DP antibodies are in pemphigus vulgaris. Methods We studied 48 sera from patients with proven pemphigus vulgaris (29 mucosal dominant pemphigus and 19 mucocutaneous pemphigus) by indirect immunofluorescence (IIF) with rat bladder epithelium (RBE) as a substrate and by immunoblotting (IB) on human keratinocyte cultures enriched in DP. Results Ten sera (21%) were positive in IIF on RBE. By IB, eight sera proved to have antibodies to both DP I (250 kDa) and DP II (210 kDa), one serum had antibodies directed to DP I only, and two sera to DP II only. Conclusions Our data confirm that RBE is not a specific IIF substrate for the serological diagnosis of PNP. It remains a sensitive and specific substrate for the detection of anti‐DP antibodies, which, in patients with pemphigus vulgaris, are probably caused by an epitope‐spreading phenomenon.     

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.     

寻常型天疱疮诊断和治疗的专家建议

寻常型天疱疮（pemphigus vulgaris,PV）是天疱疮中最常见类型,其主要特点是血清中产生针对表皮细胞间桥粒的自身抗体,临床表现为松弛性水疱、大疱,伴有顽固性、痛性黏膜糜烂和溃疡,组织病理出现特征性棘层松解现象。PV治疗的主要目的是控制病情,促使皮损和黏膜尽快愈合,减少治疗的不良反应和提高患者的生活质量,力争长期缓解,直至痊愈。治疗的挑战在于长期稳定控制病情、减少复发、避免长期应用糖皮质激素（简称激素）和免疫抑制剂的不良反应,减少激素用量。由于该病较少见,大样本随机、双盲、安慰剂对照的前瞻性研究较少。欧洲和日本已经形成了自己的治疗共识,但目前我国尚无类似共识形成。本文在综合不同国家和地区共识性文献的基础上,结合中国国情,经国内不同地区的专家反复讨论修订,形成了PV的诊断和治疗指导性意见和建议……     

Neonatal pemphigus vulgaris

A male newborn with skin erosions was born to a 32-year-old woman who was under treatment for pemphigus vulgaris that had been diagnosed 16 months earlier. Antibodies to desmoglein (Dsg)1 and Dsg3 were analyzed by enzyme-linked immunosorbent assay. Index values of antibodies to Dsg1 and Dsg3 were 49 (normal index values, <14) and 121 (normal index values, <7), respectively. Those findings concluded a diagnosis of neonatal pemphigus vulgaris. No new vesicles or bullae appeared in the newborn after the birth. Non-corticosteroid ointments produced prompt epithelialization on the erosive lesions. All the eruptions disappeared in 3 weeks. The level of serum anti-Dsg3 autoantibodies when measured at the 76th day was negative (<5).     

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.     

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.     

Ocular involvement in pemphigus vulgaris

Pemphigus vulgaris (PV) is an autoimmune disorder affecting the skin and mucous membranes. Ocular involvement in PV has been reported but its prevalence and clinical characteristics are not well defined. This prospective cross‐sectional study of 103 PV patients was designed to determine the prevalence, clinical types and epidemiological trends of ocular involvement in a population of Iranian patients with PV. Ocular involvement was present in 17 (16.5%) patients. Conjunctivitis was the most prevalent type of ocular involvement (9/17, 52.9%), followed by erosion of the palpebral conjunctiva (7/17, 41.2%). Erosion of the bulbar conjunctiva was noted in only one patient (5.9%). The most commonly reported symptoms were eye irritation (76.5%) and redness (76.5%). No significant relation was found between ocular involvement and disease activity (partial remission or relapse). Mucoid discharge was significantly more common in patients with conjunctival erosions as compared to patients with conjunctivitis (P = 0.038). We conclude that ocular involvement is not rare in PV; 16.5% of PV patients develop ocular disease independent of the disease activity and extension. Conjunctivitis is the most common type of involvement, however, palpebral conjunctival erosion is more frequent than previously realized.     

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.     

Simultaneous onset of pemphigus vulgaris in two Turkish siblings

The etiology of pemphigus vulgaris is still unknown. Reported familial cases are indicators of a genetic aspect of the disease. We report a brother and sister with simultaneous onset of pemphigus vulgaris. The class II antigens, HLA DRB1*04 and DQB1*03 were detected in both patients. The oral mucosa was affected in one them. Elevation of transaminase levels due to azathioprine therapy was observed in these two cases.     

Neonatal pemphigus vulgaris with extensive mucocutaneous lesions from a mother with oral pemphigus vulgaris

The clinical phenotype of pemphigus is well explained by the combination of desmoglein (Dsg) 1 and Dsg3 distribution pattern and antiDsg autoantibody profile (Dsg compensation theory). It has been reported that neonatal skin has a similar Dsg distribution pattern to adult mucosal epithelia. We describe a newborn girl with mucocutaneous pemphigus vulgaris (PV) from a mother with mucosal dominant PV. The mother had had painful oral erosions for at least 7 months. Histopathological examination and direct and indirect immunofluorescence studies confirmed the diagnosis of PV and neonatal PV in the mother and daughter, respectively. The mother had a high titre of anti-Dsg3 IgG and a low titre of antiDsg1 IgG, while the neonate had only a high titre of anti-Dsg3 IgG, but no detectable antiDsg1 IgG. AntiDsg3 IgG, which caused the oral dominant phenotype in the mother, induced extensive oral as well as cutaneous lesions in the neonate. Our case provides clinical evidence for the Dsg compensation theory in neonatal PV.