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Background Since 1967 dermatology has used the classic technique of indirect immunofluorescence (IFI) for the detection of autoantibodies against antigens of the skin in diseased people with endemic pemphigus foliaceus. Thirty years later enzyme-linked immunosorbent assays – ELISA (rDsg1 and rDsg3) appeared as a viable option. A group of highly recognized researchers have concluded that ELISA is a simple, sensitive and highly specific method, allowing for diagnostic differentiation between pemphigus vulgaris (PV) and endemic pemphigus foliaceus (EPF). Scientific literature certifies that both ELISA and IIF bear high sensitivity in spite of the fact that a direct comparison between the ELISA and IIF tests has never been performed. Objectives This study was conducted to compare the sensitivity of these tests in detecting antibodies in the EPF. Material and methods Thirty-two serum samples were collected from patients with EPF. The control serum of 15 healthy individuals was tested to detect the presence of antibodies of EPF by indirect immunofluorescence and ELISA (rDsg1 and rDsg3). The IIF was performed, taking human skin as a substrate. Results Antibodies in patients with EPF were detected more commonly by the ELISA (rDsg1) (91%) compared with IIF (81%). Conclusions The ELISA (rDsg1) is slightly more sensitive than IIF in detecting antibodies related to EPV. However, according to our results, we do not currently possess a test with 100% accuracy in differentiating EPF from PV. Although previous studies have associated Dsg3 with PV, the tests performed during this study showed that 12% (4/32) of patients with EPF (cutaneous diseases only) also had Dsg3 antibodies. [ABSTRACT FROM AUTHOR]

Summary Pemphigus is a rare autoimmune disease that results in blistering of the skin and oral cavity. It is caused by autoantibodies directed against cell-surface antigens on keratinocytes, which when targeted lose their cellular adhesion properties and separate from one another to form blisters within the epidermis. Differences in the particular antigens targeted by the antibodies and in the distribution of these antigens in the different regions of the body and in the separate layers of the epidermis result in different clinical manifestations of the disease. The disease is diagnosed based on its clinical manifestations (flaccid blisters and erosions on skin and oral mucosa), histology (epidermal acantholysis), and immunological abnormalities (circulating and tissue-fixed antibodies against keratinocyte surface antigens). Pemphigus, which if left untreated is almost always fatal, is generally managed with topical, oral, or intralesional corticosteroids. Other options include plasmapheresis and intravenous immunoglobulin (IVIg), coupled with cytotoxic drugs. Immunosupressants, anti-inflammatory drugs, and antibiotics are used as adjuvants, but apart from IVIg, these therapy options are non-specific and more research is needed to develop treatments with improved side-effect profiles. [ABSTRACT FROM AUTHOR]

Background: Melanoma is completely curable if resected early. Unfortunately, early melanoma can be difficult to differentiate from other pigmented lesions. Computerized image analysis instruments have now been developed to assist in determining whether a pigmented lesion is potentially dangerous and requires biopsy. To evaluate whether one such instrument can improve the management of pigmented lesions, we obtained biopsy specimens from 52 pigmented lesions that appeared clinically benign to an experienced dermatologist but were suspicious by image analysis. Observation: Histologically, 9 (17%) of the lesions that were removed based solely on computer recommendation were potentially dangerous and should have been removed. These included 1 malignant melanoma in situ and 8 dysplastic nevi with moderate to severe cytologic atypia. Conclusion: The results of the present study indicate that computerized image analysis can improve the evaluation of pigmented skin lesions by identifying clinically unsuspicious, but potentially dangerous, lesions that might have otherwise have been neglected. [ABSTRACT FROM AUTHOR]

Presents comments on research articles on skin diseases published in the previous issues of the periodical 'Archives of Dermatology.' Need for appropriate controls in assessing the relationship between circumcision and penile dermatoses; Incidence of chronic urticaria; Cyclosporine therapy for maintenance of remission in patients with pemphigus; Validity of the assessment of a family history of melanoma and dysplastic nevi.

Presents comments on developments in the field of dermatology from readers of the periodical 'Archives of Dermatology,' as of October 1999. Standard dermatology definitions; Use of zinc in wound repair; Use of ketamine hydrochloride on the treatment of erythrodermia-related pruritus; Use of methotrexate as an adjuvant therapy for pemphigus vulgaris.

Brazil A 2.5-month-old male infant (born by cesarean section, weighing 3650 g) received one dose of DPT vaccine (against diphtheria, whooping cough, and tetanus), one dose of SABIN vaccine, and one dose of Vaxgrip, a vaccine of purified inactivated myxovirus influenza on September 6, 1996. Five days later, he developed symmetric, pruritic, vesiculobullous lesions which began on the trunk and, over five days, progressively spread to the upper and lower extremities, hands, feet, and face. The clinical appearance is illustrated in Fig. 1. Laboratory studies performed at the time revealed a white blood cell (WBC) count of 8800, with 6% eosinophils, and negative serologic tests for syphilis and urine culture. Seventeen days following the onset of the eruption, tense blisters of varying size on erythematous bases, and occasionally in a rosette distribution at the periphery of urticarial plaques, appeared on the hands and feet and then spread to the torso and extremities. There was no mucosal involvement or systemic manifestations. The blister fluid was yellowish and cultured positive for Staphylococcus aureus. The WBC count was 34,600/mm3 with 35% eosinophils. Serum levels of immunoglobulin G (IgG) were 52 mg% (normal, 678–1714 mg%), IgA = 62.1 mg% (normal, 73–422 mg%), IgM = 81.1 mg% (normal, 54–296 mg%), and IgE = 248.7 U/ml (normal, 4.1 U/ml). Three days later, the WBC count had further increased to 55,400 with 48% eosinophils. The biopsy of a trunk lesion showed a subepidermal blister containing large numbers of leukocytes and eosinophils. The cleavage was just below the basal layer. There was a variable degree of hydropic degeneration of the basal cells. In the epidermis, there was slight spongiosis in the spinous layer and exocytosis of leukocytes, neutrophils, and eosinophils. On the epidermal side of the blister, the interpapillary crests were generally reduced, as were dermal papillae on the floor of the blister. The... [ABSTRACT FROM AUTHOR]

Antibodies to epidermal cytoplasmic antigens were present in 25 to 34% of 32 normal persons and in 34 to 50% of 53 patients with melanoma. There were at least two different types of cytoplasmic antibodies. The most common reacted to cytoplasmic antigens present only in the upper layers of the epidermis. This type of antibody occurred with equal frequency in patients with melanoma and in normal persons. The increased incidence of cytoplasmic antibodies in melanoma was due to antibodies to cytoplasmic antigens present throughout the epidermis. These antibodies were 2½ times more common in patients with melanoma than in normal persons. The presence of different cytoplasmic antigens in distinct strata of the epidermis suggests they result from epidermal cell differentiation. The epidermal cytoplasmic antigens present throughout the epidermis appear to partially cross-react with cytoplasmic antigens in melanoma cells. [ABSTRACT FROM AUTHOR]

This article focuses on the simultaneous occurrence of herpetiform pemphigus and endemic pemphigus foliaceus (fogo selvagem, FS) in a woman. A 32 year old woman from Franco da Rocha, one of the last endemic areas of FS, developed generalized FS based on clinical, histologic and immunologic criteria. Five years later, while affected with typical lesions of FS, she developed intensly puritic erthematous urticarial edematous plaques, some of which were covered with vesicles typical of herpetiform pemphigus. Histologically these lesions showed epidermal spongiosis, with eosinophilic exocytosis and acantholysis.

A 55-year-old White woman was first seen in July 1995 with ulceration of the oral mucosa, including the gingiva, labial mucosa, gums, palate and tongue, as well as erosions and blisters on the trunk. A biopsy showed a suprabasal blister with acantholysis. Direct immunofluorescence was positive for intercellular deposits of IgG and C3, and indirect immunofluorescence was positive for intercellular antibodies at a titer of 160. The patient was diagnosed as having pemphigus vulgaris and treated with prednisone 1–1.5 mg/kg/day from 1995 until 1998, but no response was observed (the disease continued to be active with the formation of new lesions). The patient developed a number of steroid-induced complications including diabetes, osteoporosis, Cushing syndrome, hypertension and high-output cardiac failure, and required repeated hospitalization. In August 1998 she was started on azathioprine 100–150 mg/day and continued on prednisone 1 mg/kg/day. One year later, in August 1999, the disease was still active with new lesion formation and persistent oral erosions and dysphagia, despite persistent therapy with azathioprine 150 mg/day and prednisone 1 mg/kg/day.Because of the disease severity and the lack of a response to treatment, in October 1999 the patient was started on thalidomide therapy 100 mg/day (1.7 mg/kg/day) and continued the prednisone treatment at 1 mg/kg/day together with azathioprine 150 mg/day (2.7 mg/kg/day). There was a good response, with clearing of all oral lesions in 20 days. The prednisone dose was gradually reduced and was discontinued in May 2000; azathioprine was gradually reduced to 50 mg 3 times/week (0.35 mg/kg/day). Thalidomide was continued at a dose of 100 mg/day. The patient was in total clinical remission, being free of both old and new lesions, for the next 14 months, when the thalidomide treatment was discontinued as a result of side-effects, including weakness in the legs and paresthesis of the fingers.After the discontinuance of treatment with thalidomide, severe lesions returned. Thalidomide was reintroduced, at 100 mg/day. After 2 months the patient entered total clinical remission and on the last occasion on which she was seen, in May 2003, was found to have remained clear of lesions. The patient continues to take thalidomide at 100 mg/day. [ABSTRACT FROM AUTHOR]

We present a 69-year-old white woman with pemphigus vulgaris limited to the oral mucosa who presented with oral pain and difficulty swallowing of 2 days duration, followed by multiple irregular ulcers arising from normal mucosa with no grouping of individual lesions-herpes simplex should be considered in the differential diagnosis of lesions that appear suddenly in patients with PV, particularly if the lesions fail to respond to an increased dose of corticosteroids. 1999 Elsevier Science B.V. All rights reserved. [ABSTRACT FROM AUTHOR]

The expression of U-CYT antigens, tissue-specific cytoplasmic antigens of keratinocytes that are markers of the terminal differentiation of these cells, was studied in normal skin adjacent to malignant epidermal tumors. Ten basal-cell carcinomas were studied. In all cases, it was found that the expression of U-CYT antigens in normal epidermis gradually decreased with increasing proximity to the tumors and finally disappeared completely within the tumor tissue itself. This finding suggests that basal-cell carcinoma can alter the normal differentiation of adjacent nonmalignant cells. [ABSTRACT FROM AUTHOR]

Behcet's syndrome is a multisystem disease which may produce not only the original triad of relapsing iridocyclitis and recurrent oral and genital ulceration but also skin, central nervous system, joint and gastrointestinal disease. A fatal outcome is uncommon but may occur when the central nervous system or the gastrointestinal tract is involved. We present a patient with colonic ulceration progressing rapidly to free perforation and generalized peritonitis successfully treated by emergency resection. [ABSTRACT FROM AUTHOR]

Summary: Bullous pemphigoid is an autoimmune blistering disease of the skin caused by autoantibodies directed against basement membrane zone adhesion molecules. Autoantibodies cannot fully explain several important features of the disease such as the difficulty transferring with the pathogenic autoantibodies, or the presence of heavy lesional infiltration of eosinophils and neutrophils that is necessary for disease production. There is increasing evidence that Th17 cells and the cytokines they release such as interleukin-17 are important regulators of innate and adaptive immune responses in many Th1 and/or Th2 mediated autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and allergic asthma. There is also evidence that Th17 cells have a role in pathogenesis of blistering skin diseases. Interleukin-17 is important in initiation and maintenance of many autoimmune reactions and it is involved in production of pro-inflammatory cytokines, matrix metalloproteinases, neutrophils, and eosinophils, all of which are important pathogenic factors in bullous pemphigoid. The hypothesis is that interleukin-17 has an important pathogenic role in BP and can describe features of the disease not explained by the autoantibody theory. This cytokine can be assessed in the blister fluid and sera of patients, and can be used as a marker of disease activity and response to therapy. The information obtained could also lead to the development of novel therapeutic strategies for this and other autoimmune blistering diseases. [Copyright &y& Elsevier]

The article compares the mortality of bullous pemphigoid (BP) in Europe and the US. The reported mortality of BP is much greater in Europe than in the U.S. Mortality 1 year after initiation of therapy ranges from 19% to 41% in Europe but is only 6%12% in the U.S. Studies in the U.S. are generally smaller than those conducted in Europe. However, the consistency of the reports, i.e., mortality in all European studies, is higher than in all U.S. studies, and the clear nature of the end-point (death) suggest the reported differences between European and U.S. studies are real.

A major obstacle in performing multicenter controlled trials for pemphigus is the lack of a validated disease activity scoring system. Here, we assess the reliability and convergent validity of the PDAI (pemphigus disease area index). A group of 10 dermatologists scored 15 patients with pemphigus to estimate the inter- and intra-rater reliability of the PDAI and the recently described ABSIS (autoimmune bullous skin disorder intensity score) instrument. To assess convergent validity, these tools were also correlated with the Physician's Global Assessment (PGA). Reliability studies demonstrated an intra-class correlation coefficient (ICC) for inter-rater reliability of 0.76 (95% confirdence interval (CI)=0.61–0.91) for the PDAI and 0.77 (0.63–0.91) for the ABSIS. The tools differed most in reliability of assessing skin activity, with an ICC of 0.39 (0.17–0.60) for the ABSIS and 0.86 (0.76–0.95) for the PDAI. Intra-rater test-retest reliability demonstrated an ICC of 0.98 (0.96–1.0) for the PDAI and 0.80 (0.65–0.96) for the ABSIS. The PDAI also correlated more closely with the PGA. We conclude that the PDAI is more reproducible and correlates better with physician impression of extent. Subset analysis suggests that for this population of mild-to-moderate disease activity, the PDAI captures more variability in cutaneous disease than the ABSIS. [ABSTRACT FROM AUTHOR]

The expression of bullous pemphigoid (BP) antigen in different locations on the body was estimated from the highest dilution of BP sera giving a positive reaction at a site by indirect immunofluoresconce. Three sera with high titers (640-1280) of BP antibodies against monkey and guinea pig esophagus were reacted with 46 specimens of normal human skin. There was marked variation in the expression of BP antigen in skin obtained from different sites. The greatest expression of BP antigen was in skin obtained from the flexor surfaces of the arm, leg, and thigh. All specimens from these sites reacted with high dilutions (1:640-1:2560) of BP antibodies. BP antigen was expressed least in skin specimens from scalp, face, and extensor surface of the arm. No BP antigen could be demonstrated in 17% of specimens from these locations and the remainder reacted only with low dilutions (1:40-1:160) of BP antibodies. Skin from trunk, knee, and extensor thigh had intermediate amounts of BP antigen. Similar results were seen with all 3 BP sera. Similar reactions were observed in multiple skin specimens obtained from different sites in the same individual. Of note is that the greatest expression of BP antigen was in areas commonly involved in this disease (flexural surfaces), whereas the least was seen in areas (scalp, face, extensor arm) which are rarely involved. The apparent correlation between the expression of BP antigen and the location of lesions in bullous pemphigoid, suggests that BP antigen expression may play a role in the distribution of skin lesions in this disease. [ABSTRACT FROM AUTHOR]

The expression of the pemphigus foliaceus (PF), pemphigus erythematosus (PE), and pemphigus vulgaris (PV) antigens in 16 different regions of normal human skin was evaluated by indirect immunofluorescence by using sera with a high titer of PF, PE, and PV antibodies. Regional variations were observed in the expression of all these ntigens. The expression of the PF and PE antigens, as measured by endpoint titer of antibody reactivity, was highest in skin specimens obtained from the upper torso, and lowest in those from the buccal mucosa, lower torso, and scalp. This distribution pattern differed from that of PV antigen, whose expression was highest in buccal mucosa and scalp. These patterns correlate with, and may provide a partial explanation for, the different distribution of skin lesions in these different forms of pemphigus. [ABSTRACT FROM AUTHOR]