婴儿大疱性类天疱疮1例

婴儿男,6月大时出现全身红斑、水疱和大疱,皮损组织病理可见真皮内嗜酸性细胞浸润,直接及间接免疫荧光显示:IgG基底膜带线状沉积。诊断:婴儿大疱性类天疱疮。糖皮质激素治疗有效。1岁以内婴儿大疱性类天疱疮国内报道少见。     

大疱性类天疱疮患者发根毛囊中抗体的检测

目的：通过检测大疱性类天疱疮患者拔出的头发上残留毛囊中大疱性类天疱疮抗体的沉积情况,建立一种快捷、损伤小的检测大疱性类天疱疮的方法。方法：直接免疫荧光方法测定35例大疱性类天疱疮患者拔出的头发上残留毛囊中类天疱疮抗体的沉积,10例健康人及20例天疱疮病人头发作为对照。结果：35例大疱性类天疱疮患者的毛发,其中阳性28例,阴性7例,阳性率80%;类天疱疮IgG和C3在毛囊表皮下的外毛根鞘外层与结缔组织鞘之间呈明显的线状沉积。10例正常人及20例天疱疮患者均无线状沉积。结论：本实验方法简单、快速、敏感,且具有较高特异性,有可能成为诊断和鉴别诊断大疱性类天疱疮的一种有效的方法。     

Pemphigoid Nodularis: A Case with 230 kDa Hemidesmosomes Antigen Associated with Bullous Pemphigoid Antigen

We report a 73-year-old woman with typical clinical, histological and immunofluorescence features of pemphigoid nodularis. Direct immunofluorescence studies of prurigo nodularis-like lesions and peribullous skin showed the linear deposition of IgG and C3 at the basement membrane zone. Circulating IgG against the basement membrane was also detected by indirect immunofluorescence. The serum from the patient was shown to contain the autoantibody against 230 kDa hemidesmosomal antigen associated with bullous pemphigoid antigen.     

A child with localized vulval pemphigoid and IgG autoantibodies targeting the C-terminus of collagen XVII/BP180

Localized vulval pemphigoid of childhood (LVPC) has previously been reported in six girls. Clinical features and immunopathological data have suggested it to be a morphological variant of bullous pemphigoid. Epitope targets of the autoantibodies of these patients have not been defined in detail. We describe a 9-year-old girl with possible cicatricial LVPC and circulating IgG antibodies directed against native collagen XVII/BP180, its 120-kDa soluble ectodomain and against the C-terminus of collagen XVII/BP180. No reactivity was detected towards the NC16A domain of collagen XVII/BP180. Linear IgG and C3 deposits were found along the cutaneous basement membrane zone. On 1 mol/L salt-split skin, IgG autoantibodies were shown to bind to the epidermis, and the HLA type II allele DQB1*0301, a marker with significantly increased occurrence in patients with ocular and oral cicatricial pemphigoid, was identified in this patient. Our data suggest that LVPC is a variant of bullous pemphigoid in which direct immunofluorescence microscopy combined with immunoblot analysis can deliver valuable diagnostic information for differential diagnosis. However, differentiation between the scarring and non-scarring course of the disease cannot be made with the present diagnostic markers and therefore careful follow-up of patients with LVPC is required.     

Non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans

Bronchiolitis obliterans is a small‐airway obstructive lung disease for which immunologically mediated pathogenesis is supposed. Frequent association of bronchiolitis obliterans with paraneoplastic pemphigus is well known, but its association with other autoimmune bullous diseases has not been reported except for a case of anti‐laminin‐332‐type mucous membrane pemphigoid in a patient with chronic graft‐versus‐host disease. We report a case of non‐paraneoplastic autoimmune subepidermal bullous disease associated with fatal bronchiolitis obliterans in a patient without transplantation. Although the patient's serum contained immunoglobulin (Ig)A antibodies to the 180‐kDa bullous pemphigoid antigen/type XVII collagen and IgG antibodies to laminin‐332, diagnosis of either linear IgA bullous dermatosis or mucous membrane pemphigoid could not be made because of the failure to detect linear IgA deposition at the basement membrane zone by direct immunofluorescence and the lack of mucous membrane lesions. Physicians should be aware that autoimmune bullous diseases other than paraneoplastic pemphigus can also associate with this rare but potentially fatal lung disease.     

Localized Bullous Pemphigoid of the Vulva

I report a 78-year-old female patient with multiple erosive and erythematous inflammatory lesions of the vulva of seven months duration. She was diagnosed as bullous pemphigoid based on the following findings: subepidermal blister in the histological examination, linear deposition of IgG and C3 at the basement membrane zone on direct immunofluorescence studies, and positive IgG deposition on the epidermal side of saline-split normal skin on the indirect immunofluorescence study.     

Tetracycline and niacinamide control bullous pemphigoid but not pemphigus foliaceus when these conditions coexist

Pemphigus and pemphigoid are different types of autoimmune bullous disease and can occur in the same patient. We report a female patient with this condition. At first, we diagnosed her with bullous pemphigoid, and we treated her with tetracycline, niacinamide and a topical steroid. Tense bullas disappeared shortly after that, but crusted erythemas mainly on her head and trunk persisted. We examined BP180 and desmoglein 1 enzyme‐linked immunosorbent assays, and also histological features, which showed coexistence of bullous pemphigoid and pemphigus foliaceus concurrently. Therefore, we tried prednisolone, which could control both conditions. This case showed that tetracycline and niacinamide could control bullous pemphigoid, but could not control pemphigus foliaceus, and that prednisolone was effective for both conditions.     

Anti-p200 pemphigoid responding to dapsone

Anti-p200 pemphigoid is a rare autoimmune subepidermal blistering disease. Clinical presentation is similar to standard bullous pemphigoid (BP) but mucous membranes and cephalic lesions are more frequent. Histology and direct immunofluorescence (IF) are identical to BP but indirect IF discloses linear deposits of immunoglobulin G (IgG) on the dermal side of artificial salt-split skin. Specific diagnosis is based on western immunoblotting that shows circulating IgG recognizing a 200-kDa protein localized on the dermal extract. The 200-kDa antigen was recently identified as laminin γ1. Anti-p200 pemphigoid should be considered before all atypical or topical steroid-resistant bullous disease, as well as mucous membranes pemphigoid or epidermolysis bullosa acquisita. Dapsone appears to be the most effective treatment and should be used as the first option in combination with topical steroids. In this report, we describe the case of a patient with a typical clinical and immunopathological anti-p200 pemphigoid, responding to a combination of topical steroids and dapsone.     

Pemphigoid with antibodies to laminin γ1, BP180 and BP230, associated with psoriasis vulgaris: Successful disease control with cyclosporin

Both anti‐laminin γ1 pemphigoid and bullous pemphigoid are autoimmune subepidermal blistering diseases. The former is rare and characterized by autoantibodies to laminin γ1, a 200‐kDa dermal protein, while the latter is common among the elderly and characterized by autoantibodies to BP180 and BP230, both of which are hemidesmosomal proteins. We experienced a 69‐year‐old Japanese male patient with blister formation secondary to erythrodermic psoriasis, which was successfully treated with cyclosporin. The histopathology of erythema corresponded with psoriasis and that of a blistering lesion showed infiltration of neutrophils and eosinophils in and around the subepidermal blisters. Patient immunoglobulin G antibodies labeled both the epidermal and dermal sides of 1 mol/L NaCl‐split human skin by indirect immunofluorescent microscopy and recognized laminin γ1, BP180 and BP230 by immunoblotting. To the best of our knowledge, this is the first report of coexistence of psoriasis and atypical pemphigoid with these three autoantibodies.     

Coexistence of Pemphigus and Bullous Pemphigoid

Widespread tense blisters developed on a 60-year-old Japanese man who had been diagnosed with pemphigus 11 years earlier, because of a history of pruritic erythema and erosions on his face, chest, and back, mild supra-basal layer blister formation found in a biopsy specimen, and a positive direct immunofluorescence test showing IgG deposition in the intercellular space. The histological findings showed subepidermal blister, and the immunoblot study detected 180kD bullous pemphigoid antigen. Direct immunofluorescence test revealed intercellular staining for IgG, and indirect immunofluorescence tests repeatedly demonstrated the presence of circulating antibodies to the intercellular space. From these observations, this case suggests the coexistence of pemphigus and bullous pemphigoid.     

Erythrodermic bullous pemphigoid is a clinical variant of bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering disease of the skin. Several variants olBP have been described but until recently the relationship of these variants to generalized BP was unclear. Several studies have shown that pemphigoid nodularis, pemphigoid vegetans, localized BP and vesicular pemphigoid are true variants of BP as the circulating antibodies in these patients recognize the same 230kDa BP antigen as found in patients with generalized BP. Erythrodermic BP is a very unusual variant characterized by an erythroderma along with blister formation. We describe the third known patient to develop erythrodermic BP and characterize the antigenic specificity of the circulating antibodies in both our newly reported patient with erythrodermic BP and in one of the two other previously reported cases of erythrodermic BP. Both patients with erythrodermic BP had circulating IgG antibodies which bound to the epidermal side of salt-split human skin in a pattern identical to two patients with immunopathologically proven generalized BP. Sera from four erythrodermic patients without blisters and from a healthy normal volunteer, as controls, failed to demonstrate detectable circulating IgG autoantibodies. Immunoprecipitation studies revealed that both patients with erythrodermic BP had circulating IgG autoantibodies which recognized, to varying degrees, the same 230 and 180kDa BP antigens as recognized by sera from two patients with immunopathologically proven generalized BP. Sera from four erythrodermic patients without blisters and from a healthy normal volunteer, as controls, failed to recognize any specific polypeptides. These observations demonstrate that erythrodermic BP is a distinct clinical variant of BP.     

Drug-induced bullous pemphigoid with dermal fluorescence on salt-split skin

The immunological features of drug-induced bullous pemphigoid appear to be similar to those of idiopathic bullous pemphigoid (BP), with presence of circulating and tissue-bound antibodies showing anti-basement membrane zone specificity. We describe a 28-year-old woman who developed a widespread blistering eruption with marked involvement of the mucous membranes shortly after commencing treatment with oral flucloxacillin. The eruption gradually cleared following drug withdrawal and treatment with oral corticosteroids. Indirect immunofluorescence showed circulating IgG anti-basement membrane zone (BMZ) antibody and C3 which bound to the dermal aspect of salt-split skin, and direct immunofluorescence (IMF) of perilesional skin showed a linear band of C3 at the BMZ. Western immunoblotting of the patient's serum showed positive reactivity with a 180 kDa antigen in epidermal extracts and no reactivity with dermal extracts. The dermal-binding pattern on indirect IMF with salt-split skin only occurs in a minority of patients with BP and has not been described previously in a drug-induced case.     

Characterization of the antibody response in oesophageal cicatricial pemphigoid

Cicatricial pemphigoid (CP) is a subepidermal, autoimmune bullous dermatosis. It is classified as a clinical subset of bullous pemphigoid (BP). However, it differs from BP in some significant ways: (i) in CP mucosal involvement with clinical scarring is prominent; (ii) there is a prominent IgA class antibody response alone or in addition to the IgG class antibody response; and (iii) there is a heterogeneous antibody response in CP, whereas in BP the majority of the antibodies are directed against a 180-kDa hemidesmosomal protein, bullous pemphigoid antigen 2 (BPAg2). Oesophageal involvement in CP is a rare, but often devastating manifestation. In this study we examined the humoral autoimmune response in oesophageal CP, in an attempt to characterize the autoantibody reactivity profile. We used direct and indirect immunofluorescence and Western immunoblotting using normal human skin and oesophagus substrates. We studied patient sera over time in order to search for evidence of epitope spreading in these patients. All patients had positive direct immunofluorescence of perilesional oesophageal epithelium. All patients had positive circulating antibasement membrane zone autoantibody titres. There was a significant IgA class in addition to an IgG class autoantibody response. IgA and IgG antibodies demonstrated significant reactivity with BPAg2 and the 97 kDa linear IgA disease antigen on Western immunoblot suggesting intraprotein epitope spreading. There was no evidence of interprotein epitope spreading over time. Our findings suggest that there is a heterogeneous antibody response in oesophageal CP with the predominant antigen being BPAg2.     

Pemphigoid nodularis with IgA autoantibodies against the intracellular domain of desmoglein 1

Pemphigoid nodularis is a rare variant of bullous pemphigoid. We report a 49-year-old Japanese male with clinical and histopathological features of pemphigoid nodularis including circulating and in vivo-bound IgG antibasement membrane zone antibodies and IgA anti-intercellular antibodies. Although the precise molecular target of the IgG autoantibodies could not be determined, intriguingly, immunoblotting showed that the IgA in the patient's serum reacted with the intracellular domain of desmoglein 1, the target antigen in cases of pemphigus foliaceus. However, the IgA did not react with the extracellular domain of desmoglein 1 in sensitive enzyme-linked immunosorbent assay studies using a baculovirus system. These results suggest therefore that these IgA antibodies may possibly not be pathogenic. The mechanism for the production of different autoantibodies is unknown, but this case provides further illustration of the atypical skin immunoreactants often seen in this unusual subtype of bullous pemphigoid.     

Refractory bullous pemphigoid leaving numerous milia during recovery

Recovery with milia may occur in bullous pemphigoid (BP), mucous membrane pemphigoid (MMP) and epidermolysis bullosa acquisita (EBA). Scarring commonly occurs in MMP and EBA. Here, we report a 62‐year‐old man patient with BP, who was left with numerous milia during recovery. The patient had immunoglobulin (Ig)G autoantibodies to the recombinant protein of the BP180‐NC16a domain and the soluble 120‐kDa ectodomain of BP180 (linear IgA bullous dermatosis [LAD]‐1). There are cases of BP with IgG autoantibodies to LAD‐1 and/or the recombinant protein of BP180 C‐terminal domain. Extensive milia formation during recovery may be associated with immunological predisposition and/or improper interaction between hemidesmosomes and the extracellular matrix components.     

药物相关性大疱性类天疱疮研究进展

药物相关性大疱性类天疱疮(drug-associated bullous pemphigoid,DABP)特指应用特定药物诱发的一种特殊类型的类天疱疮,其临床表现、组织学或免疫病理特征与特发性大疱性类天疱疮相同或相近。近年由药物导致大疱性类天疱疮的报道增多,本文就DABP的研究进展进行综述。     

Cicatricial pemphigoid with linear IgA deposit

A Japanese woman with typical clinical and histological manifestations of cicatricial pemphigoid was presented. Direct immunofluorescent (IF) investigation of perilesional skin revealed in vivo deposits of IgA but not of IgG, IgM, or C3. Indirect IF study revealed that this patient had circulating antibody against epidermal basement membrane zone of the IgA class. We would like to classify this case as cicatricial pemphigoid with IgA deposits rather than as a cicatricial variant of linear IgA bullous dermatosis.     

Bullous Pemphigoid Associated with Shy-Drager Syndrome

We report a patient with Shy-Drager syndrome who developed multiple tense blisters mainly on the extremities. Circulating anti-basement membrane zone autoantibodies were detected by the indirect immunofluorescence method. Immunoblot analysis using normal human epidermal extracts demonstrated that this patient's serum reacted only with 230 kD bullous pemphigoid antigen (BPAG1). Concerning the pathoetiology of the association of bullous pemphigoid and Shy-Drager syndrome, we discuss a sequence similarity between BPAG1 and dystonin, a candidate gene for dystonia musculorum.     

Erythrodermic lichen planus pemphigoides

Lichen planus pemphigoides is a clinico-histological subtype of lichen planus in which there are bullous lesions similar to those of bullous pemphigoid. Lichen planus is included among the rare causes of erythroderma. We present a case of erythrodermic lichen planus pemphigoides in a 49-year-old female patient who satisfactorily responded to treatment with cyclosporine. A detailed physical examination and immunofluorescence study are key to the diagnosis of lichen planus pemphigoides.     

U-serrated immunodeposition pattern differentiates type VII collagen targeting bullous diseases from other subepidermal bullous autoimmune diseases

BACKGROUND: Epidermolysis bullosa acquisita (EBA) can be differentiated from other subepidermal bullous diseases by sophisticated techniques such as immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping, immunoblot and enzyme-linked immunosorbent assay. OBJECTIVES: To determine whether the diagnosis can also be made by routine direct immunofluorescence microscopy. METHODS: We studied frozen skin biopsies from 157 patients with various subepidermal immunobullous diseases. RESULTS: We found three distinct 'linear' fluorescence patterns at the basement membrane zone: true linear, n-serrated and u-serrated. The true linear pattern, often seen in conjunction with either the n- or the u-serrated pattern, was found in any subepidermal immunobullous disease with nongranular depositions. In bullous pemphigoid, mucous membrane pemphigoid, antiepiligrin cicatricial pemphigoid, p200 pemphigoid and linear IgA disease the n-serrated pattern was found, corresponding with depositions located in hemidesmosomes, lamina lucida or lamina densa. However, in EBA and bullous systemic lupus erythematosus the u-serrated staining pattern was seen, corresponding with the ultralocalization of type VII collagen in the sublamina densa zone. The diagnosis of EBA with IgG or IgA autoantibodies directed against type VII collagen was confirmed by immunoelectron microscopy, salt-split skin antigen mapping, fluorescence overlay antigen mapping or immunoblotting. CONCLUSIONS: Using this pattern recognition by direct immunofluorescence microscopy we discovered several cases of EBA which would otherwise have been erroneously diagnosed as a form of pemphigoid or linear IgA disease.