W. Ray Gammon

Immunofluorescence on split skin for the detection and differentiation of basement membrane zone autoantibodies

The autoimmune subepidermal bullous diseases are characterized by autoantibodies to the basement membrane zone of stratified squamous epithelium. Recent studies have shown that the antibodies have characteristic ultrastructural and antigenic binding properties and that differentiating between those properties can be useful in distinguishing one disease from another. Immunofluorescence microscopy is widely used to detect basement membrane zone autoantibodies. The test has traditionally used tissue substrates with an intact basement membrane zone. Those substrates are limited because autoantibody binding cannot always be detected and because autoantibodies with different ultrastructural and antigenic binding properties cannot be distinguished from each other. Normal human skin that has been separated through the basement membrane zone (i.e., split skin) has recently been used as a substrate for detecting and characterizing basement membrane zone autoantibodies by immunofluorescence. Studies indicate that split skin is a more sensitive substrate than intact skin for detecting the antibodies and that antibodies with different ultrastructural binding sites can often be differentiated from one another on split skin. Those studies suggest split skin is the substrate of choice for the routine immunofluorescence evaluation of autoimmune subepidermal bullous diseases.

Epidermolysis bullosa acquisita presenting as an inflammatory bullous disease

A patient is described with the histologic, immunohistologic, and immunoelectron microscopic features of epidermolysis bullosa acquisita (EBA). Although she eventually developed the clinical features of that disease, she differs from previously reported patients by initially having an inflammatory dermatoses and a generalized erythematous bullous eruption clinically indistinguishable from bullous pemphigoid. The presentation suggests that the clinical spectrum of EBA may include a generalized inflammatory bullous disease and that EBA should be considered in the differential diagnosis of chronic acquired inflammatory bullous dermatoses.

Mechanism of lesion production in pemphigus and pemphigoid

Current evidence strongly supports the theory that the lesions of pemphigus are due to binding of pemphigus antibody to an antigen in or near the epidermal cell membrane, which causes a release of at least one enzyme which results in dissolution of the intercellular attachments and acantholysis. Similarly, strong evidence supports the hypothesis that pemphigoid blisters are due to binding of antibody at the basement membrane, followed by activation of complement and release of anaphylatoxins which activate tissue mast cells to release eosinophil chemotactic factor. These eosinophils then release tissue-destructive enzymes and reactive oxygen intermediates directly onto the basement membrane zone, with loss of dermoepidermal adherence and formation of blisters.

Bullous systemic lupus erythematosus: An unusual clinical course and detectable circulating autoantibodies to the epidermolysis bullosa acquisita antigen

Bullous systemic lupus erythematosus is a newly recognized form of systemic lupus erythematosus characterized by a skin eruption clinically and histologically resembling dermatitis herpetiformis and responsive to dapsone. We report on a patient with bullous systemic lupus erythematosus who initially presented with lesions clinically resembling erythema multiforme, experienced exacerbation of her disease with dapsone, and had detectable circulating autoantibodies to the epidermolysis bullosa acquisita antigen.

Clearing of epidermolysis bullosa acquisita with cyclosporine

Abstract Epidermolysis bullosa acquisita is a chronic, severe, subepidermal, blistering disease of the skin, characterized by marked resistance to topical and systemic therapy. This report concerns a well-documented case of a woman who had had epidermolysis bullosa acquisita for 6 years and had remained hospitalized continuously for 7 months in 1987. Her case ultimately was controlled with cyclosporine after the failure of a variety of therapeutic modalities in the hospital, including prednisone, methotrexate, azathioprine, phenytoin, vitamin E, gold sodium thiomalate (Myochrysine), isotretinoin, and plasmapheresis. In contrast to patients with pemphigus and pemphigoid treated with cyclosporine, our patients autoantibodies did not disappear on therapy. Although its mechanism of action in epidermolysis bullosa acquisita is unknown, we propose that cyclosporine may be a helpful drug for patients whose disease is refractory to more traditional forms of therapy.

Bullous eruption of systemic lupus erythematosus

Chronic vesiculobullous eruptions are relatively uncommon in systemic lupus erythematosus (SLE). Their incidence among patients with skin lesions has been estimated at less than 5% [1–3]. Blistering eruptions in SLE can be divided into three categories. The first includes a number of primary blistering diseases that have been reported in association with SLE. These include bullous pemphigoid (BP) [4–9], dermatitis herpetiformis (DH) [10–14], pemphigus vulgaris/foliaceous [15–20], epidermolysis bullosa acquisita (EBA) [21, 22], erythema multiforme [23, 24], porphyria cutanea tarda [25], toxic epidermal necrolysis [26] and dystrophic epidermolysis bullosa [27]. Each of these diseases has its own diagnostic features and the association with SLE is generally regarded as fortuitous and not a specific manifestation of SLE. Many of the primary blistering diseases are associated with autoimmune features that may be difficult to distinguish from the cutaneous immunological features of SLE.

Direct immunofluorescence microscopy of 1 mol/L sodium chloride-treated patient skin

Patients with bullous pemphigoid and those with epidermolysis bullosa acquisita often demonstrate virtually identical clinical, histologic, and immunopathologic features. Although some patients can be distinguished by their pattern of circulating IgG anti-basement membrane zone antibody binding to 1 mol/L sodium chloride-split human skin, approximately 20% and 50% of bullous pemphigoid and epidermolysis bullosa acquisita patients, respectively, do not possess such antibodies. Hence this study sought to determine whether these patients can be distinguished by mapping the distribution of basement membrane zone immunoreactants in patient skin split in vitro by 1 mol/L sodium chloride. All sodium chloride-treated samples from patients with bullous pemphigoid (n = 8), epidermolysis bullosa acquisita (n = 4), or other bullous skin diseases (n = 6) contained a lamina lucida cleavage plane bounded by bullous pemphigoid antigen and laminin; moreover, treatment of patient samples was performed without loss of tissue substrate or in situ immunoreactants. Deposits of IgG were found on the epidermal side of sodium chloride-treated skin from 13 of 14 bullous pemphigoid samples; IgG deposits in bullous pemphigoid samples were exclusively epidermal in eight, epidermal and dermal in five, and solely dermal in one. In contrast, IgG was found exclusively on the dermal side of sodium chloride-treated samples from patients with epidermolysis bullosa acquisita. Although IgG mapping distinguished bullous pemphigoid and epidermolysis bullosa acquisita patients in 94% of these samples, the distribution of C3 in sodium chloride-treated patient skin was more variable and less predictive diagnostically.(ABSTRACT TRUNCATED AT 250 WORDS)

In vivo suppression of neutrophil chemotaxis by systemically and topically administered tetracycline

In vivo suppression of neutrophil chemotaxis in humans by orally and topically administered tetracycline (TCN) was examined using both modified Boyden chamber and skin chamber assays. Chemoattractants were derived from serum complement and bacterial culture supernates. The results showed that oral TCN caused significant suppression of neutrophil chemotaxis when measured by both assays and both sources of chemoattractant. Furthermore, application of a commercially available topical preparation containing TCN caused local suppression of chemotaxis as measured by the skin chamber assay. These results show that TCN does suppress neutrophil migration in vivo, and they provide support for an anti-inflammatory effect of TCN mediated in part by suppression of neutrophil chemotaxis.

Childhood epidermolysis bullosa acquisita: Report of three cases and review of literature

Epidermolysis bullosa acquisita is an acquired subepidermal blistering disease with variable clinical, pathologic, and immunologic features. The disease has been reported infrequently in adults and only rarely in children. We describe three new cases of childhood epidermolysis bullosa acquisita, review three previously reported cases, and contrast the features of the disease in children with those in adults. The results suggest that both children and adults with epidermolysis bullosa acquisita have variable clinical and pathologic features that may mimic other bullous diseases. Epidermolysis bullosa acquisita is characterized by a chronic course, poor response to therapy, and occasional clinical remissions.

Comparative efficacy of oral erythromycin versus oral tetracycline in the treatment of acne vulgaris. A double-blind study.

The efficacy of erythromycin base (E-Mycin tablets, 333 mg) and the efficacy of tetracycline hydrochloride (Panmycin tablets) were compared in this double-blind, randomized study. Two hundred patients with moderate to moderately severe acne vulgaris were randomly assigned to the study. One hundred patients received 1 gm of erythromycin base by mouth per day for 4 weeks, followed by 333 mg/day for 8 weeks, plus placebo for tetracycline. The second group of patients received 1 gm of tetracycline by mouth per day for 4 weeks, followed by 500 mg/day for 8 weeks, plus placebo for erythromycin. Both drugs reduced acne severity to the same extent. Pustules, papules, and open comedo counts decreased significantly over the 12-week period. Seventy-seven percent of the erythromycin-treated patients and 89% of the tetracycline-treated patients stated that their acne was markedly improved or improved by week 12. Most of the side effects in patients treated with erythromycin were gastrointestinal symptoms. Among the side effects in patients treated with tetracycline were Candida vaginitis in one patient and pseudotumor cerebri in one patient.