Unusual variants of pemphigoid: from pruritus to pemphigoid nodularis

We report three patients with pemphigoid nodularis. Patients were females aged 76, 71 and 50 years, and all had features of bullous pemphigoid together with prurigo-like lesions at some stage of their illness. In two cases, nodular lesions preceded the onset of blistering by some months. Blisters arose on normal skin and in one patients also at sites of prurigo lesions. Routine histology of bullous lesions revealed the presence of subepidermal blisters. Electron microscopy performed in two cases confirmed the level of split to be through the lamina lucida. Direct immunofluorescence in all cases was positive, with linear basement membrane zone deposition of IgG and C3. Circulating IgG anti-basement membrane antibody was also detected in all patients, and in two, immunoblotting revealed a single antigen of 220 kD.     

Indirect complement immunofluorescence in the immunopathological assessment of bullous pemphigoid, cicatricial pemphigoid, and herpes gestationis

Sera from 50 untreated patients with bullous pemphigoid were examined by both the customary method of indirect immunofluorescence using anti IgG conjugate and by indirect complement immunofluorescence using anti C₃ conjugate to detect circulating antibasement membrane zone antibodies. A circulating antibasement membrane zone antibody could be detected by the IgG method in 58% and by the C₃ method in 76%. Sera from six patients with cicatricial pemphigoid examined in the same way showed a circulating antibasement membrane zone antibody in one by the IgG method but in three by the C₃ method of indirect immunofluorescence. Sera from ten patients with active herpes gestationis contained anti-basement membrane zone antibody demonstrable by the C₃ method in every case and by the IgG method of indirect immunofluorescence in one of these. Basement membrane zone bound IgG, or more commonly C₃ in a linear pattern, was shown by direct immunofluorescence in all patients with bullous or cicatricial pemphigoid from whom adequate biopsy material was obtained. The immunopathological similarities of bullous pemphigoid, cicatricial pemphigoid and herpes gestationis are stressed, and the usefulness of indirect complement immunofluorescence in their diagnosis is emphasized.     

Bullous pemphigoid: the frequency of mucosal involvement and concurrent malignancy related to indirect immunofluorescence findings

A review of 124 cases of bullous pemphigoid was made and the clinical findings correlated with the results of indirect immunofluorescence. A circulating IgG basement membrane zone (BMZ) antibody was detected in the serum of eighty-nine (72%) of the patients. Antibody titres in these patients did not correlate with the extent of the disease or with the presence of mucous membrane lesions. Indeed, oral lesions were more common in the thirty-five sero-negative patients with 17% of such patients being affected compared to only 10% of those with positive indirect immunofluorescence findings. This difference, however, was not statistically significant. Concurrent malignant disease (i.e. malignancy occurring within 6 months of pemphigoid being diagnosed) occurred in eight of the seronegative group (23%) and in only four of the eighty-nine seropositive cases (4%); this difference was significant. The association of bullous pemphigoid and malignant disease still remains controversial, but those who believe that the relationship is coincidental must now explain why concurrent malignant disease is more common in patients who have bullous pemphigoid and negative indirect immunofluorescence findings.     

Frequency of IgA antibodies in pemphigus, bullous pemphigoid and mucous membrane pemphigoid

Circulating and bound IgA antibodies can be found in the autoimmune blistering diseases, but their prevalence, clinical relevance and target antigens remain unknown. Thirty-two patients with pemphigus, 73 with bullous pemphigoid and 28 with mucous membrane pemphigoid were studied retrospectively. Direct immunofluorescence (DIF) analysis of IgG, IgA, IgM and C3 was carried out for all cases. Sera were studied by standard indirect immunofluorescence, indirect immunofluorescence on salt-split skin, immunoblotting for bullous pemphigoid and mucous membrane pemphigoid and ELISA for pemphigus. With DIF, we found IgA autoantibodies in 22 of all 133 cases. Circulating IgA antibodies to skin were detected in 2 of 3 IgA-DIF-positive patients with pemphigus, in 3 of 6 with bullous pemphigoid, and in 6 of 13 with mucous membrane pemphigoid. We confirm that the IgA reactivity is more frequently associated with mucous membrane involvement, especially in cases without critical involvement (5/8). The role of IgA and its antigenic specificity in these diseases remain unclear.     

Cutaneous involvement in localized forms of bullous pemphigoid

In summary, there is much overlap among the three types of localized cutaneous pemphigoid discussed. They all tend to affect the same age group, in general. They all may remain regional or be associated with a generalized eruption consistent with bullous pemphigoid. These three variants of subepidermal blistering disease also appear to be susceptible to koebnerization. Direct immunofluorescence findings are identical, as well, with linear IgG and C3 at the basement membrane. Indirect immunofluorescence tends to be negative for all three variants, with a tendency to positivity with increased extent and severity of skin involvement. There are differences, though, between them. BPP tends to affect men more than women, unlike BMMP-CP and localized cutaneous nonscarring BP. Localized cutaneous nonscarring BP usually involves the legs, whereas the other two conditions affect the head and neck, with resultant scarring. Histology is similar to that seen in BP, but dermal fibrosis and sclerosis result in skin affected by BMMP-CP and BPP. Localized cutaneous nonscarring BP is more amenable to topical steroid therapy, whereas BMMP-CP and BPP are more persistent and resistant to systemic immunosuppressive therapy. Clinical, histologic, and immunologic similarities among the pemphigoid variants may reflect common antigenic features. On the other hand, clinical, histologic, and immunologic differences may imply that there are more than one bullous pemphigoid antibody directed at a variety of antigenic structures.     

Two cases of subepidermal blistering disease with anti-p200 or 180-kD bullous pemphigoid antigen associated with psoriasis

We describe two patients with psoriasis vulgaris who subsequently developed a subepidermal blistering disease which disclosed IgG and C3 at the basement membrane zone in direct immunofluorescence. The first case was a 75-year-old Japanese man with herpetiform lesions. Histopathology showed neutrophil infiltration. IgG antibodies bound to the dermal side of the salt-split skin. Immunoblot analysis identified a 200-kD antigen in dermal extracts. The second case was a 70-year-old Japanese man. Histopathology showed eosinophil infiltration. IgG antibodies bound to the epidermal side of salt-split skin. Immunoblot analysis identified a 180-kD bullous pemphigoid (BP) antigen in epidermal extracts. We review the clinical and pathological features of psoriatic patients who presented a subepidermal blistering disease in which antigens were detected by immunoblot analysis; i.e., anti-p200 pemphigoid (14 cases) or BP (12 cases). There were few distinct clinical differences between two diseases. However, neutrophils were predominant in anti-p200 pemphigoid, while eosinophils were predominant in BP. After blister formation, ciclosporin was used effectively in addition to systemic steroids in the treatment of anti-p200 pemphigoid. On the other hand, ciclosporin was not used in the treatment of BP with psoriasis.     

The distribution of IgG subclasses in pemphigoid gestationis: PG factor is an IgG1 autoantibody

Using monoclonal antibodies in immunofluorescence techniques, the subclass distribution of anti-basement membrane zone IgG antibodies was studied in the skin, placenta, and serum of patients with pemphigoid (herpes) gestationis. IgG1 was found to be the major IgG subclass in both serum and tissue, being detected in the sera of all pemphigoid gestationis patients studied. In pemphigoid and pemphigus, however, the distribution of IgG subclasses was heterogeneous, with IgG4 being the dominant autoantibody. Pemphigoid (herpes) gestationis factor, the circulating anti-basement membrane zone autoantibody thought to be pathogenic in pemphigoid gestationis, is therefore, an IgG1 antibody, with inferred complement binding capacity. Tissue damage in pemphigoid gestationis is apparently mediated by complement fixation which is detected via the classical complement cascade.     

Concomitant Occurrence of Circulating IgA Anti-intercellular and Anti-basement Membrane Zone Antibodies in Autoimmune Blistering Diseases: Immunofluorescence and Immunoblot Studies

Recently, cases with circulating IgA anti-intercellular antibodies have been described. The objective of this study was to present immunofluorescence and immunoblot findings in three cases of bullous diseases with concomitant circulating IgA anti-intercellular and anti-basement membrane zone antibodies. Direct immunofluorescence, indirect immunofluorescence on intact and 1M NaCl-split skin, immunoblotting of epidermal extracts from dispase- and EDTA-separated (two different procedures) human skin, and immunoblotting of the bovine desmosome preparation were performed. All three cases had IgA anti-intercellular and anti-basement membrane zone antibodies. However, immunoblot results were divergent. Case 1 had antibodies against the 150 kD pemphigus foliaceus antigen (IgG), the 170 kD protein (IgG and IgA), and the 97 kD antigen (IgG and IgA). Case 2 had IgG antibodies reactive with the 230 kD and the 170 kD bullous pemphigoid antigens, while case 3 had IgA antibodies against the 97 kD antigen only. The results of immunofluorescence and immunoblot studies in our patients widen the spectrum of laboratory features in blistering skin diseases mediated, at least in part, by antibodies of the IgA class.     

无水疱性类天疱疮一例

患者，男，70岁。全身泛发多形性红斑、丘疹伴瘙痒3个月，未见水疱。皮肤病理示真皮浅层血管周围轻度淋巴细胞、嗜酸粒细胞浸润。直接免疫荧光示表皮细胞间及基底膜IgG、C3、IgM、IgA阴性。间接免疫荧光示抗基底膜带IgG抗体1:40阳性。正常人皮肤盐裂间接免疫荧光示IgG表皮侧阳性。诊断为无水疱性类天疱疮，给予烟酰胺、四环素、雷公藤多苷口服，配合外用卤米松乳膏治疗，2个月后皮损基本消退。     

Polymorphic pemphigoid.

We describe 20 patients with a chronic polymorphic eruption; they shared clinical, histopathological, and therapeutic features of both dermatitis herpetiformis and bullous pemphigoid (BP). In 14 of these 20 cases, direct and indirect immunofluorescence studies corresponded to BP. The remaining six patients showed IgA deposits in a linear pattern at the basement membrane zone, and two of these six showed IgA pemphigoid antibodies in their sera as well. No significant clinical and histological differences were detected in the patients, in connection with the immunological findings. Furthermore, one patient's condition, which was studied by repeated immunofluorescence examinations, changed from a linear IgA pattern and a negative indirect test to a linear IgG pattern and a positive reaction for IgG pemphigoid antibodies. We concluded that these cases constitute a polymorphic variant of BP.     

Childhood vulval pemphigoid: a clinical and immunopathological study of five patients

We describe five girls with vulval pemphigoid: two had bullous pemphigoid confined to the vulva and three had cicatricial pemphigoid. They demonstrate a spectrum of severity from localized disease to extensive vulval scarring necessitating long-term immunosuppressive therapy and surgical correction. The age at onset of their disease ranged between 6 and 13 years. All presented with vulval discomfort and erosions. Three had oral lesions, two perianal and one eye and cutaneous involvement. Two girls with only vulval lesions and one with vulval and oral lesions responded well to topical steroids. In two, systemic treatment with prednisolone and dapsone or azathioprine was required. The diagnosis was made on the basis of histology and immunofluorescence (IF). All had positive direct IF with IgG and C3. Indirect IF demonstrated circulating IgG binding to the basement membrane zone in four, with dermal or epidermal binding on salt-split skin substrate. Immunoblotting revealed antibodies to the BP230 and BP180 antigens. Immunoelectron microscopy in the child with dermal binding IgG and BP180 and BP230 on immunoblotting showed labelling at the lamina densa-lamina lucida interface adjacent to hemidesmosomes.     

2825例皮肤病患者皮损直接免疫荧光检查结果分析

目的为了探讨直接免疫荧光检查对某些皮肤病的意义。方法采用抗人Ｉｇ（ＩｇＧ、ＩｇＡ、ＩｇＭ和补体Ｃ３）直接免疫荧光技术对２８２５例（８９个病种）皮肤病患者皮损作了检查。结果９２６例系统性红斑狼疮皮损区基底膜阳性占９５％,曝光区正常皮肤基底膜阳性占８０％,而２８７例盘状红斑狼疮皮损基底膜阳性占９２％,曝光区正常皮肤均阴性;６２例混合结缔组织病皮损区阳性为８５％;１８４例皮肌炎皮损血管壁阳性７０％;７３例系统性硬皮病皮损区阳性７０％;２１１例寻常型银屑病皮损区角质层阳性９３％;１２５例寻常性天疱疮皮损区表皮细胞间阳性９５％;８５例大疱性类天疱疮的阳性为９２％;７１例疱疹样皮炎的阳性为９０％;１１６例血管炎病灶区血管壁阳性为９０％。结论提示ＳＬＥ、ＤＬＥ及大疱性皮肤病皮损的免疫荧光标记形态具有特征性改变。而且,直接免疫荧光检查对其它皮肤病的诊断与鉴别诊断也有重要意义。     

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.     

大疱性类天疱疮患者血清总IgE与血清自身抗体的关系

目的 分析大疱性类天疱疮患者血清总IgE与抗BP180IgG抗体、抗BP230IgG抗体、抗表皮基底膜IgG抗体滴度(即间接免疫荧光滴度)的关系.方法 收集沈阳市第七人民医院2014年1月-2020年1月大疱性类天疱疮病例,进行回顾性分析,根据抗BP180IgG抗体、抗BP230IgG抗体阳性情况将患者分组,比较组间血...     

Coexistence of lichen planus and bullous pemphigoid (an immunofluorescence study of a "lichen pemphigoides") (author's transl)]

A 35 year old black man presented with a generalized eruption of lichen planus; subsequently tense blisters appeared within the lichenoid lesions and on clinically normal skin. Histopathological characteristics of lichen planus were present in the papules, and those of bullous pemphigoid were seen in the bullae taken from non-lichenoid skin. Direct immunofluorescence studies revealed immunological characteristics of lichen planus in skin and mucosal lesions of L. P. Bound IgG and beta1 C/beta1 A with tubular patterns were detected at the dermo-epidermal junction in all the skin fragments (clinically normal skin, bullous lesions lichenoid skin and mucous lesions). Indirect immunofluorescence studies showed at several intervals that the patient had circulating antibasement membrane zone antibodies (IgG; titres 1/50). This is the third published case in which immunofluorescence studies have established the "pemphigoid" nature of some bullous lichen planus. These findings are in favour of an immune disorder in lichen planus.     

Bullous pemphigoid and multiple sclerosis: more than a coincidence? Report of three cases

In three patients with long-standing multiple sclerosis, bullous pemphigoid developed. The diagnosis of bullous pemphigoid was based on histologic findings, direct and indirect immunofluorescence, and Western blots showing IgG reacting with the 220 to 240 kD bullous pemphigoid antigen in the serum of three patients. Contrary to previous observations, bullous pemphigoid associated with multiple sclerosis was not different from bullous pemphigoid alone. Three similar cases have been reported previously, so the occurrence of bullous pemphigoid in patients with multiple sclerosis may be more than a coincidence.     

Localized pemphigoid

Of 144 patients with buUous or cicatricial pemphigoid, nine with localized pemphigoid were seen at the Mayo Clinic between 1968 and 1975. In two patients the disease had become generalized before presentation, and in one it had evolved into bullous pemphigoid, the only case with positive indirect immunofluorescence. One additional patient showed mucosal lesions. Direct immunofluorescence was performed in flve patients and showed linear deposition of C3 and fibrin but not immunoglobulins in three; in two patients immunofluorescence was negative. Localized pemphigoid can be divided into two types: that with scarring plaque-like lesions usually occurring on the head and neck predominantly in males, and that with localized bullous lesions usually occurring on the lower part of the legs of females.     

Mucosal involvement in bullous and cicatricial pemphigoid. A clinical and immunopathological study

Thirty-six patients with bullous pemphigoid (BP) and 15 with cicatricial pemphigoid (CP) were studied for evidence of mucosal involvement both clinically and by direct immunofluorescence. Twenty-one patients with BP and all those with CP had lesions of the mucous membranes. Eighteen patients with BP and 14 patients with CP had involvement of the oral mucosa. Lesions of the eyes, nose, pharynx, vulva and urethra also occurred in both groups. The lesions tended to be more widespread in CP patients. Twenty-one patients with BP and 14 with CP were examined by an ophthalmologist. Fine scarring of the tarsal conjunctiva was found in both groups, but also in elderly controls. However, symblepharon occurred in one patient with BP as well as in three patients with CP, but was not seen in a group of 20 controls. Direct immunofluorescence (IF) studies showed linear deposition of IgG or C3 or both in the basement membrane zone of the skin, oral mucosa and conjunctival mucosa in both groups. The frequency of positive immunofluorescence was higher in the conjunctiva than in the lip mucosa or skin in both BP and CP patients. The significance of these findings and the relationship between BP and CP is discussed.     

A case of anti-epiligrin cicatricial pemphigoid associated with lung carcinoma and severe laryngeal stenosis: review of Japanese cases and evaluation of risk for internal malignancy

A 68-year-old Japanese male with a five-year-history of lung carcinoma showed recurrent blisters and erosions on the oral and genital mucosae and the skin. The patient complained of dyspnea due to severe laryngeal stenosis and underwent a tracheostomy. A skin biopsy specimen showed a subepidermal blister and linear deposits of IgG and C3 at the basement membrane zone of the epidermis. Indirect immunofluorescence examination demonstrated circulating IgG anti-basement membrane zone autoantibodies that reacted to epiligrin on immunoblotting. Based on a diagnosis of anti-epiligrin cicatricial pemphigoid, he was treated with prednisolone, minocycline hydrochloride and nicotinamide. Although no new skin lesions appeared, he died of lung carcinoma five months after the tracheostomy. A review of reported cases with anti-epiligrin cicatricial pemphigoid in Japan disclosed that 5 of 16 cases (31.2%) were complicated by internal malignancies.     

结节性类天疱疮七例临床病理分析

目的 回顾分析结节性类天疱疮的临床特点。方法 回顾分析7例结节性类天疱疮患者的性别、发病年龄、临床表现及治疗和随访情况。结果 7例结节性类天疱疮患者中,女4例、男3例,发病年龄中位值59岁。临床表现以痒疹样皮损、结节为主,伴或不伴水疱,瘙痒症状明显,确诊前均误诊为结节性痒疹、湿疹。所有患者病理表现均有表皮增生肥厚,可见表皮下裂隙,真皮乳头胶原增生,浅层血管周围淋巴细胞、嗜酸性粒细胞浸润;直接免疫荧光检查基底膜带IgG和C3呈线状阳性,间接免疫荧光有2例阳性。7例联合使用糖皮质激素和免疫抑制剂治疗有效。结论 结节性类天疱疮临床易误诊,免疫病理检查有利于诊断,糖皮质激素和免疫抑制剂治疗有效。