Arnold L. Schroeter

The late phase of the immediate wheal and flare skin reaction. Its dependence upon IgE antibodies.

IgE antibodies are usually thought to induce only immediate skin reactions. We have shown that the intradermal injection of a number of different allergens can produce a prolonged inflammatory reaction after the immediate wheal and flare in most sensitive subjects. This late inflammatory response occurs 6-12 h after challenge and is characterized by diffuse edema, erythema, pruritus, and heat. Both immediate and late responses can also be seen after passive sensitization of skin sites in nonatopic subjects. That IgE is involved in inducing the reaction was shown by the abolition of both immediate and late responses by passive transfer tests in the following experiments: (a) heating atopic serum at 56degreesC for 4 h, (b) removing IgE from the atopic serum by a solid phase anti-IgE immunoabsorbent, and (c) competitively inhibiting the binding of IgE antibodies to cells by an IgE myeloma protein. In addition, both responses were induced by affinity chromatography-purified IgE antibody, followed by antigenic challenge. Very similar lesions could also be induced by intradermal injection of Compound 48/80, thus suggesting a central role in the reaction for the mast cell or basophil. Histologically, the late phase is characterized by edema and a mixed cellular infiltration, predominantly lymphocytic but also containing eosinophils, neutrophils and basophils. Direct immunofluorescent staining did not show deposition of immunoglobulins or complement components, except IgM in 2 of 15 and C3 in 1 of 15 patients. This finding indicates that the late phase does not depend on the deposition of immune complexes. The results of the study suggest that IgE-allergen interaction on the surfaces of mast cells or on infiltrating basophils causes both immediate and late cutaneous responses.

Histopathologic and immunopathologic study of pyoderma gangrenosum

Sixty‐three patients with pyoderma gangrenosum were seen and studied at the Mayo Clinic from 1971 to 1980. Biopsies from the erythcmatous border or necrotic edge of the pyoderma gangrenosum lesions usually demonstrated a characteristic pathogenic morphologic evolution. The early lesions revealed mild to moderate perivascular lymphocytic infiltrate associated with endothelial swelling. The fully developed lesions demonstrated necrosis in addition to a dense lymphocytic infiltration surrounding as well as involving the blood vessels. Extravasation of erythro‐cytes and thrombosis sometimes were seen. Ulceration, infarction, and abscess formation were found in the later stages of evolution. Direct immunofluorescence results were positive in the blood vessels of 36 of 65 (55%) specimens. IgM, C3, and fibrin were found in the papillary and retieular dermal vessels. IgG and IgA were only occasionally present. Pyoderma gangrenosum appears to be a reactive process that is manifested as a vasculilis. Biopsy material from the advancing active erylhc‐matous border has early characteristic derniatopathologic findings of lymphocytic vasculitis. Cutaneous vascular immune deposits suggest an immune pathogenesis of either an immune complex disease or lymphocytotoxic reaction.

Pacemaker contact sensitivity

In a patient who had 4 cardiac pacemakers implanted and removed, pruritus, redness, and swelling of the skin overlying the pacemaker developed at intervals of 6 weeks to 17 months after insertion. Patch testing showed a 2 + reaction to titanium. The positive result of this test, the titanium case of the generator, and the history of multiple local reactions around the generator site pointed toward contact sensitivity to the pacemaker. Although a review of the literature indicates that this problem is rare, it is of extreme importance to the patient with pacemaker contact dermatitis.

The clinical and histopathologic spectrums of urticarial vasculitis: Study of forty cases

Urticarial skin lesions may occur in patients as a manifestation of necrotizing vasculitis. We describe a series of forty patients with idiopathic chronic urticaria and histologic features of necrotizing vasculitis. On the basis of clinical evaluation, we have classified urticarial vasculitis into two major groups: (1) hypocomplementemic (sixteen patients, ten of whom had evidence of renal disease) and (2) normocomplementemic (twelve patients with systemic disease and twelve with only cutaneous involvement). Most patients with hypocomplementemia presented with arthritis, and some had abdominal pain or airway compromise. Although patients with normocomplementemia and systemic disease had a less severe clinical course, four exhibited renal disease that was characterized by microhematuria and proteinuria. Direct immunofluorescence microscopy of the skin aids in assessing renal involvement in some cases of hypocomplementemic urticarial vasculitis, particularly when IgG and IgM are deposited at the basement membrane. There seems to be a spectrum of disease in urticarial vasculitis, ranging from benign cutaneous lesions to systemic disease.

Double-blind crossover study comparing doxepin with diphenhydramine for the treatment chronic urticaria

Fifty patients with chronic idiopathic urticaria were studied to compare responses to treatment with doxepin (10 mg three times a day) and with diphenhydramine (25 mg three times a day). All patients had an evaluation that failed to disclose a cause for their disease. Therapeutic response was assessed according to the suppression of symptoms and symptom diary scores of daily itching and frequency, number, size, and duration of hives. Total clearing of the pruritus and urticarial lesions occurred in 43% of the patients while receiving doxepin and in only 5% while receiving diphenhydramine (p less than 0.001). Partial or total control of the pruritus and hives was noted in 74% of the patients receiving doxepin and in only 10% of those receiving diphenhydramine (p less than 0.001). Doxepin induced markedly less sedation (22%) than diphenhydramine (46%) (p less than 0.05). Dermatopathologic categories included (1) urticaria simplex, (2) lymphocytic urticaria, and (3) leukocytoclastic urticaria. Patients with urticaria simplex had a more favorable response to doxepin than the two other groups.

The complement system in bullous pemphigoid. II. Immunofluorescent evidence for both classical and alternate-pathway activation

Abstract Skin lesions of 15 bullous pemphigoid patients were examined for the presence of Clq, C3, C3 proactivator (C3PA), and properdin in addition to immunoglobulins (IgG, IgA, and IgM) and fibrin using immunofluorescent (IF) techniques. Properdin and C3 were present along the skin basement-membrane zone in all of the lesions studied in addition to immunoglobulins. Deposition of C3PA was found in only 5 of 15 skin speciments with considerably less staining intensity than that observed for C3 and properdin. Deposition of Clq was present in 12 of 15 skin lesions while fibrin deposition was present in 11 of 15 skin lesions. Absorption of anti-C3PA and antiproperdin with C3PA and properdin, respectively, blocked the specific staining reactions. These studies, therefore, suggest local activation of complement, by both the classical and alternate pathways, in bullous pemphigoid skin lesions.

AN UNUSUAL VARIANT OF LUPUS ERYTHEMATOSUS OR LICHEN PLANUS

Four patients with a similar eruption of distinct livid plaques are presented. Clinically, the lesions were difficult to diagnose as either lichen planus or lupus erythematosus. However, histological studies with standard and immunofluorescence staining methods were more consistent with lichen planus. In contrast, certain laboratory findings and the clinical course were suggestive of lupus erythematosus.

Henoch-Schönlein vasculitis: Direct immunofluorescence study of uninvolved skin

Henoch-Schönlein purpura is a multisystem disease believed to be a consequence of entrapment of circulating IgA-containing immune complexes in blood vessel walls throughout the skin, kidney, and gastrointestinal tract. In this direct immunofluorescence study, twenty-five skin biopsy specimens from twenty patients with Henoch-Schönlein purpura were examined (9 from uninvolved, normal-appearing skin). A distinct stippled pattern of vascular fluorescence was found in 87% of lesion biopsies; 75% of these contained deposits of IgA. In uninvolved skin, seven (78%) showed immunoglobulin in vessel walls and six (67%) contained IgA, suggesting that immune complexes are deposited with equal frequency in normal-appearing and lesional skin of patients with Henoch-Schönlein purpura. Biopsy of uninvolved, rather than of purpuric, skin for direct immunofluorescence studies may be more helpful in confirming the diagnosis of Henoch-Schönlein purpura because tissue morphology is usually of better quality.

Effectiveness of Intravenous Immunoglobulin Therapy for Skin Disease Other Than Toxic Epidermal Necrolysis: A Retrospective Review of Mayo Clinic Experience

OBJECTIVE To examine retrospectively the use and effectiveness of intravenous immunoglobulin (IVIg) treatment of various skin diseases, primarily immunobullous disease. PATIENTS AND METHODS We identified patients who had received IVIg therapy for skin disease between 1996 and 2003 at the Mayo Clinic in Rochester, Minn, Scottsdale, Ariz, and Jacksonville, Fla, and retrospectively reviewed their medical records. RESULTS Eighteen patients were treated with IVIg for various skin diseases: immunobullous disease in 11 adults (pemphigus vulgaris [7 patients], bullous pemphigold [3], and cicatricial pemphigoid [1]); dermatomyositis (2); mixed connective tissue disease (1); chronic urticaria (1); scleromyxedema (1); leukocytoclastic vasculitis (1); and linear IgA bullous disease (1). Responses of patients by type of disease were as follows: pemphigus vulgaris, 1 partial response (PR) and 6 no response (NR); bullous pemphigoid, 1 complete response (CR) and 2 NR; cicatricial pemphigoid, 1 NR; dermatomyositis, 1 CR and 1 PR; mixed connective tissue disease, 1 CR; chronic urticaria, 1 CR; scleromyxedema, 1 CR; leukocytoclastic vasculitis, 1 PR; and linear IgA bullous disease, 1 CR. Six patients (33%) experienced CR, 3 (17%) had PR, and 9 (50%) had NR to IVIg therapy. All 9 nonresponders were adult patients with immunobullous disease. CONCLUSION Although this was a retrospective study of a small cohort of a mixture of patients, the findings emphasize that our experience with IVIg treatment for skin disease, particularly immunobullous disease, is less favorable than that reported previously. Further studies are needed to verify the efficacy of IVIg for skin disease.

Cyclosporine in the Treatment of Dermatologic Disease: An Update

Treatment with cyclosporine is beneficial for many dermatologic diseases such as psoriasis, lichen planus, Behçet disease, atopic dermatitis, pyoderma gangrenosum, and epidermolysis bullosa acquisita. The selective action of cyclosporine on helper T cells and its rapid therapeutic action and weak myelotoxicity are the key advantages in the treatment of many dermatologic diseases. Nevertheless, drug toxicity, especially nephrotoxicity, high rates of relapse after treatment cessation, and high cost have limited its use to those diseases refractory to other therapies. Herein we discuss the use of cyclosporine for dermatologic diseases relative to efficacy, dosage, safety profile, and monitoring. In addition, we review the formulations and metabolism of cyclosporine; discuss its mechanism of action, clinical indications in dermatology, and side effects; and provide usage guidelines for this drug. Cyclosporine can be safely administered when potential toxicities, dosing, and monitoring guidelines are known.