Three difficult cases: the challenge of autoimmunity, immunodeficiency and recurrent infections in patients with Good syndrome.

Good syndrome (GS) is a rare, adult-acquired primary combined immunodeficiency syndrome arising in the context of previous or current thymoma. Patients with GS frequently develop recurrent sinopulmonary infections and are also at high risk of autoimmune manifestations, including skin conditions such as lichen planus. We report three middle-aged patients with GS complicated by multiple autoimmune and infectious manifestations. The combination of immunodeficiency, autoimmunity and recurrent infections seen in patients with GS continues to present a management challenge, particularly in patients with oral mucosal disease and recurrent candidiasis. Clinicians should be prompted to investigate an underlying immunodeficiency in patients with multiple autoimmune conditions and recurrent sinopulmonary infections.

Conjunctival involvement in cicatricial and bullous pemphigoid: a clinical and immunopathological study.

Patients with bullous pemphigoid were found to have significant ocular abnormalities. In a group of 18 patients one had conjunctival shrinkage, and 11 of 15 (73%) had positive linear direct immunofluorescence on conjunctival biopsy from a clinically uninvolved site. Our ocular findings in a group of 14 with cicatricial pemphigoid are also reported and compared with those from a control group of 20. Our findings suggest there is overlap between the pemphigoid groups and raise further questions about the pathogenicity of immunoreactants within the basement membrane zone. Bulbar conjunctival biopsy was simple and well tolerated, and the rate of immunofluorescence positivity of conjunctiva was twice that of skin in both pemphigoid groups.

Human papillomaviruses in anogenital warts in children: typing by in situ hybridisation.

OBJECTIVE: To identify the types of human papillomaviruses found in anogenital warts in children and to relate these to clinical and social information. DESIGN: In situ hybridisation using biotin labelled DNA probes to 11 types of human papillomavirus was performed on biopsy specimens from 17 children with anogenital warts. SETTING: Nuffield department of pathology and the department of dermatology, Oxford. PATIENTS: Children in one group were referred by general practitioners or paediatricians to the dermatology department, where biopsies were performed. The other children were seen in four different hospitals, and biopsy specimens were submitted to the laboratory at the physician's or pathologist's request. RESULTS: Of the 17 biopsy specimens, 10 contained cells positive with a probe to a genital human papillomavirus type (types 6 or 11), while six were positive with a skin virus type (types 2 or 3). One was negative. The virus type present bore no relation to the site or appearance of the warts. The virus type did, however, appear to correlate with groups of children. Skin types were commoner in older children (over 4 years), in those with a relative who had skin warts, and in children with warts elsewhere; there was no relation with the child's sex and no suspicion of sexual abuse in these children. These circumstances suggested non-sexual transmission, such as autoinoculation. In contrast, genital types were commoner in girls, in children under 3 years, in children with relatives with genital warts, and in those with no warts elsewhere. Nevertheless, there was suspicion or evidence of sexual abuse in only half these children, suggesting that other routes of transmission--for example, perinatal--might have been implicated. CONCLUSION: Anogenital warts in children may contain either skin or genital wart virus type. Although the type of human papillomavirus present may give some indication of the likely mode of transmission, this can be interpreted only in conjunction with all available clinical and social information. The type of virus does not provide proof of the presence or absence of sexual transmission.

The association of bullous pemphigoid and malignant disease: a case control study.

In a case control study, the incidence of malignant disease in 84 patients with bullous pemphigoid (BP) was compared with 168 controls. The rate of malignant disease (past, concurrent or during follow-up) in BP patients was 17.9% compared to 5.3% in the controls. A number of the malignancies occurring in the BP group may be of doubtful significance, being either temporally very remote or partially attributable to treatment. The rate of concurrent BP and malignancy (within 8 weeks) was 6.0% suggesting that there is probably a slight excess of malignancy in BP, but insufficient to warrant extensive investigation in pursuit of cancer. Comparison of the BP patients with and without cancer identified no clinical or immunopathological subgroups in whom investigations would be indicated. Three patients with both BP and malignancy were HLA-DR 13 positive, which may point to an immunogenetic predisposition to both diseases.

Pemphigus.

Pemphigus is an autoimmune blistering disorder. Paradoxically intact blisters are rarely seen as the superficial blister is so fragile. The disease is frequently fatal if untreated. Pemphigus is an ideal model for autoimmunity as the antigen has been characterized and the antibody demonstrated to be pathogenic.

Patterned androgenic alopecia in women.

Recession of the frontal and frontoparietal hair line in women has been regarded as a marker for pathologic virilization. In a clinical survey of 564 normal women in the population, frontal and frontoparietal recessions were found in 13% of premenopausal and in 37% of postmenopausal women. Patterned hair loss in women is commoner than hitherto described, particularly after the menopause. In the absence of other signs of virilization, "male-pattern" hair loss would therefore appear to be a poor indicator of gross abnormality of androgen metabolism.

Lack of predictive factors for the clinical course of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is a clinically heterogeneous disease although little is known of the factors affecting its course and outcome. OBJECTIVE: Our purpose was to document the clinical course, outcomes, and causes of death in treated bullous pemphigoid and to determine the predictive factors affecting outcome. METHODS: The clinical course was documented in 82 patients with immunologically proven bullous pemphigoid (mean follow-up 3 years 2 months). To identify factors predictive of outcome, 16 patients with "good prognosis bullous pemphigoid" (no systemic treatment or in remission within 2 years) were compared with 12 patients with recurrent disease requiring maintenance therapy who still needed treatment after 3 years or longer. Remission was defined as 3 months free of lesions, without systemic treatment. RESULTS: The disease duration varied from 9 weeks to 17 years (estimated median treatment time 2 years 1 month). Of patients followed up for at least 2 years, 30% achieved remission and by 3 years the remission rate was 50%. Two patients had a subsequent relapse (9%). The mortality rate at 1 year was 19%, and treatment was believed to be contributory in seven deaths. No clinical, immunologic, or immunogenetic factors were predictive of disease duration. CONCLUSION: Despite the heterogeneity of the clinical course and duration of bullous pemphigoid, no predictive factors are recognized.

Post-mammoplasty human adjuvant disease.

Morphoea and keratoconjunctivitis sicca developed in a woman with seronegative rheumatoid arthritis six years after augmentation mammoplasty. Previous reports of post-mammoplasty connective tissue disease have followed the use of silicone gel, whereas the more 'biologically inert' saline-filled silastic implants were used in this case.

Primary cutaneous anaplastic large-cell lymphoma with a prolonged erythrodermic prodrome.

Anaplastic large cell lymphoma (ALCL) is a high grade non-Hodgkins lymphoma recognized by the expression of the CD30 marker and by its morphology. We report a patient with a 6-year history of a non-specific erythroderma in whom ALCL developed with rapid and fatal dissemination to the lymph nodes and internal organs.

An immunohistochemical study of the distribution of plasminogen and plasminogen activators in bullous pemphigoid.

Abnormalities of the cutaneous plasminogen/plasminogen activator system have been associated with acantholytic disorders, psoriasis, keratinocytes in culture, and epidermis in healing wounds. The present study was undertaken to investigate the possible role of the plasmin/plasminogen protease system in lesion development in bullous pemphigoid (BP). Using polyclonal antibodies and a fluorescent technique, the immunohistochemical distribution of plasmin/plasminogen, fibrinogen and the plasminogen activators, urokinase (uPA) and tissue plasminogen activator (tPA), were studied in lesional and non-lesional skin from nine BP patients, one with linear IgA disease (LAD) and one with pemphigoid gestationis (PG). The distribution of the proteases was compared with that in normal skin (n = 4) and in suction blisters (n = 2). In normal skin, fibrinogen, tPA and uPA were absent from the epidermis and plasminogen was confined to the basal layer. Uninvolved BP skin was identical to controls. Focal areas of suprabasal plasminogen expression in the region of a blister was seen in 3/9 BP lesions and in 1/2 suction blisters. In 6/9 BP lesions and both uninvolved and lesional LAD and PG skin were identical to controls, and no suprabasal expression of plasminogen was present. These findings suggest that suprabasal plasminogen expression is unlikely to play a fundamental role in the pathogenesis of blister formation in BP as enhanced expression was not present in every case and the finding was not specific to BP, also occurring in a suction blister. Enhanced plasminogen expression rather may be a reflection of the processes of tissue repair.

Dapsone as first line therapy for bullous pemphigoid.

In an open study, a total of 18 patients with proven bullous pemphigoid (16 new patients and two in relapse) were treated with a trial of dapsone (17 patients) or sulphonimide (one patient). Overall, eight patients were controlled on one of these agents as the sole treatment (44%). Six patients had a partial, but inadequate response, while four did not respond. The responses to the sulpha drugs were generally rapid, i.e. within 2 weeks, and the maximum doses used in any patient were 100 mg/day dapsone and 1.5 g/day of sulphapyridine or sulphamethoxypyridazine. Significant side-effects to dapsone occurred in six of the 17 patients. A trial of a sulphone or sulphonamide drug is warranted in bullous pemphigoid both as an initial treatment or in the treatment of relapse, particularly when there is a contraindication to the use of corticosteroids. Side-effects are common and therapy needs to be closely monitored.

Absence of expression of class II major histocompatibility complex determinants on keratinocytes in bullous pemphigoid.

Aberrant expression of class II products of the major histocompatibility complex (HLA-D locus antigens) occurs on keratinocytes in several inflammatory dermatoses and on thyroid epithelial cells in autoimmune thyroiditis. The functional significance of aberrant HLA-D expression is unclear but it has been hypothesized that epithelial cells bearing these determinants may act as antigen-presenting cells for autoantigens. The aim of the present study was to investigate the pathogenesis of bullous pemphigoid using immunohistochemical methods to determine whether the HLA-D locus antigens are aberrantly expressed on keratinocytes in lesional and uninvolved skin. A panel of monoclonal antibodies to each of the HLA-D subregions (DR, DP and DQ) and to Langerhans cells was used. Epidermal expression of the HLA-D locus antigens was similar in patients and controls, and there was no significant increase in expression in lesional skin compared with uninvolved skin in six out of nine patients. In three out of nine patients slight enhancement of epidermal HLA-D expression in lesional epidermis corresponded to increased Langerhans cells rather than expression on keratinocytes. HLA-D locus antigens are absent from keratinocytes in bullous pemphigoid skin and aberrant expression of these determinants cannot therefore be implicated in antigen presentation.

Bullous pemphigoid: correlation of mucosal involvement and mucosal expression of autoantigens studied by indirect immunofluorescence and immunoblotting.

Twenty patients with bullous pemphigoid were studied prospectively: sequential sera, in different phases of the disease, were collected over a period of approximately 2 years. The sera were tested using standard immunofluorescence techniques with salt-split and intact human tissue from different sites of the body (thigh, breast, oral mucosa, vagina); an early serum of each patient was tested by Western blotting. The concentration of circulating antibodies detected by the intact skin and intact mucous membranes was similar; split tissue was more sensitive than intact tissue. For eight of 19 patients, split vagina and occasionally split oral mucosa (in the same patients) were much less sensitive than all other tissues. Furthermore, there was a correlation between autoantibody reactivity with split mucous membrane tissues and clinical mucosal involvement. These results strongly suggest heterogeneity of antigens or epitopes expressed between tissues. In both split skin and mucosa all sera consistently detected an antigen on the epidermal side of the split regardless of the stage of the disease. Immunoblotting studies showed no correlation between specific antigens and mucosal expression or skin involvement.

HLA type in bullous pemphigoid, cicatricial pemphigoid and linear IgA disease.

In a study of 32 patients with bullous pemphigoid (BP), 16 patients with cicatricial pemphigoid (CP) and 10 patients with linear IgA disease (LAD) no significant association was found between these diseases and HLA type of the A, B, C and DR loci. In order to determine whether HLA type modified the clinical expression of these subepidermal diseases, the results were analysed for any association with mucosal involvement, the presence of scarring or the occurrence of a circulating anti-basement membrane zone antibody. No significant associations were found.

Tattoo removal using infra-red coagulation: a dose comparison.

Using an infra-red coagulator, 42 tattoos were treated using pulses of 1.125 s (27 tattoos) or 1.25 s (15 tattoos). Treatment failures occurred only in three professional tattoos. Amateur tattoos were satisfactorily treated in over 80% of cases regardless of dose. Deeper collagen necrosis occurred with 1.25 s, but scarring was clinically similar. Pre-treatment biopsy to assess pigment depth was of no value in selection of the optimum pulse duration and increased the complication rate. The possible mechanism of pigment removal is discussed.

The distribution of alpha 6 beta 4 integrins in lesional and non-lesional skin in bullous pemphigoid.

The alpha 6 beta 4 integrin is associated ultrastructurally with the hemidesmosomes of the basal keratinocytes and with the bullous pemphigoid antigen (BPA), suggesting an important role in adhesion of epidermal cells to the basement membrane. Using an immunofluorescence technique with chain-specific monoclonal antibodies to the alpha and beta subunits we have investigated the distribution of the alpha 6 beta 4 integrin in normal skin (n = 3) and in BP skin (uninvolved, perilesional and lesional) [n = 11]). The findings have been compared with other types of subepidermal blisters and with normal skin split by chemical means (n = 2) and by suction (n = 2). The distribution of alpha 6 beta 4 integrin was compared with that of bullous pemphigoid antigen (BPA) and with other basement membrane zone (BMZ) macromolecules, laminin, collagen type IV, collagen type VII and the BM600 antigen. In uninvolved, perilesional and early pre-blistered lesional BP skin the distribution of both the alpha 6 and beta 4 integrin subunits, BPA laminin, collagen types IV and VII and the BM600 antigen was identical to normal skin, i.e. a linear band in the BMZ. Within BP blisters, both alpha 6 and beta 4 integrin subunits and BPA were absent, except in two blisters in which the integrin expression was retained in the blister roof, despite loss of BPA. The other BMZ components were expressed on the blister floor.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical expression of bullous pemphigoid is not determined by the specificity of the target antigen.

The major bullous pemphigoid (BP) antigen is a 220-240-kDa polypeptide, although some BP sera recognize bands of 180-200 kDa or lower molecular weight. We have investigated to what extent this heterogeneity of the target antigen accounts for the clinical diversity of BP. Immunoblotting studies against extracts of salt-separated epidermis were performed on sera from 39 patients with BP. The blotting patters obtained were correlated with the clinical findings, with particular reference to prodromal itching, lesion morphology and severity, mucosal involvement, presence of milia, dapsone responsiveness and disease duration. The results confirm that the major BP antigen is a 220-kDa polypeptide, and that the 180-kDa polypeptide is a second and sometimes the sole BP antigen identified in immunoblots. Rarely, multiple bands of lower molecular weight were found. There was no correlation between the pattern of BP antigens detected in immunoblots and the clinical presentation and course of BP. There was considerable clinical diversity even among the nine patients showing specificity for a single 220-kDa target antigen. Although two patients with a single 180-kDa antigen specificity had a disease of unusually long duration, factors other than antigen specificity must determine the clinical expression of BP.