Biomedical subjects
Publications and source records attributed to A L Schroeter.
Indirect immunofluorescence testing was carried out on sera from 14 patients with cicatricial pemphigoid with use of both autologous and homologous human tissue substrates. The results were largely negative. The sensitivity of detection of circulating antibody is not increased with these substrates over that with animal tissue substrates.
In a group of 93 patients with generalized bullous pemphigoid seen at the Mayo Clinic from 1970 to 1980, the frequency of concomitant malignancies did not appear to be higher than in the general population or in previously reported series from the Mayo Clinic. However, the subgroup with negative indirect immunofluorescent tests had an unexplained higher frequency of malignancy (4/28) than the subgroup with positive immunofluorescent tests (5/65).
Seven of forty-two patients with livedoid vasculitis whose cases were reviewed at the Mayo Clinic were found to have abdominal aortic disease, in the form of aortic calcification and atherosclerosis or aneurysm. None of these patients had any associated systemic mesenchymal disease (lupus erythematosus, periarteritis nodosa, rheumatoid arthritis, Sjögren's syndrome, or carcinomatous diseases). Three patients received graft replacements for aneurysm or vascular occlusive disease. Removal of the aneurysm in one case was associated with resolution of the livedoid vasculitis. Abdominal aortic changes should be considered in patients with diagnosed livedoid vasculitis.
Four patients with recurrent attacks of angioedema, urticaria, and fever were seen. During attacks, body weights increased up to 18% and leukocyte counts reached 108,000/microliters (88% eosinophils). Glucocorticoid therapy caused defervescence, diuresis, and decreased total leukocyte and eosinophil counts. The two children received prednisone intermittently; the adults did not require treatment or their conditions were controlled by alternate-day prednisone administration. No patient had evidence of cardiac involvement (follow-up, 2-17 years). The disease does not threaten the function of vital organs. One patient remained in spontaneous remission for 20 years before symptoms recurred. Although it might be classified as a variant of the hypereosinophilic syndrome, we believe that this syndrome is a separate entity because of its distinctive characteristics and its benign course.
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Neuroendocrine carcinomas of the skin have recently been recognized, and clinicopathologic information on these tumors is accumulating rapidly. We studied 13 such lesions by light and electron microscopy, and eight were subjected to immunohistochemical analysis. The ages of the patients (five women and eight men) ranged from 24 to 84 years. Nine patients had neoplasms occurring in sun-exposed areas; one patient had metachronous symmetric lesions on the arms, and another had antecedent hypohidrotic ectodermal dysplasia. Eight tumors metastasized, and six spread to regional or distant lymph nodes. Three patients died with visceral metastases to the liver, bones, and brain. All patients had their primary tumor confined to the corium and subcutaneous tissue without involvement of overlying epidermis. Tumor cells were round and uniform in size, with delicate nuclear chromatin and a high mitotic rate. An organoid growth pattern was seen in all tumors, with focal trabeculation and rare rosette formation. Ultrastructurally, peripheral cytoplasmic dense-core granules were evident, and perinuclear filament whorls could be seen in all 13 tumors. The latter feature was stable, even in specimens taken from paraffin blocks for electron microscopy. Immunoperoxidase studies failed to reveal serotonin, calcitonin, or adrenocorticotrophin within tumor cells.
The role of the eosinophil in the pathogenesis of cutaneous diseases is not known. The eosinophil granule major basic protein (MBP), constituting the core and accounting for greater than 50% of the eosinophil granule, is toxic to helminths and mammalian cells. To determine whether eosinophil degranulation occurs in lesions of chronic urticaria, we performed an indirect immunofluorescence assay on sections of formalin-fixed, paraffin-embedded tissue, utilizing affinity chromatography-purified antibody to MBP. Twelve of 28 biopsies showed evidence of degranulation as judged by the deposition of MBP outside the eosinophil. The positive staining was of 3 types: (1) small blood vessel walls (5 patients), (2) dispersion of granular material (9 patients), and (3) focal or diffuse immunofluorescence of connective tissue fibers (11 patients). These results suggest a possible role for the cytotoxic molecule MBP in the evolution of lesions of chronic urticaria.
Direct immunofluorescence was done in fifty-one cases of pyoderma gangrenosum. Biopsy specimens were taken from the peripheral erythematous zone of the lesion. In thirty-one cases (61%), there was positive immunofluorescence, with perivascular deposition of immune reactants being the most frequent pattern (twenty-seven cases). These findings support a vasculitic pathogenesis of pyoderma gangrenosum.
An indirect immunofluorescence assay using formalin-fixed paraffin-embedded skin was performed on six biopsies from four patients with eosinophilic cellulitis (Wells' syndrome) to determine the extracellular localization of eosinophil granule major basic protein (MBP). Serial sections from each biopsy were treated with either affinity chromatography-purified antihuman-MBP or staphylococcal protein A purified rabbit IgG (control material). There was striking extracellular fluorescence localized to flame figures, and intracellular staining of eosinophils in all sections treated with anti-MBP as compared with controls. The pattern of MBP extracellular staining corresponded to the configuration of each flame figure (as verified by counterstain of the same section with haematoxylin and eosin). These findings show that MBP can be used as a marker for determining eosinophil degranulation and, because MBP is localized to flame figures, they suggest that MBP may play a pathogenic role in Wells' syndrome.
Bronopol (2-bromo-2-nitropropane-1, 3-diol) is an antimicrobial compound widely used as a preservative, primarily in cosmetic formulations. Analysis of patch tests performed on our patients revealed an incidence of 12.5% relevant positive results to 0.5% and/or 0.25% bronopol. This result reflects a history of prolonged use of bronopol-containing lubricants in our referral population of patients with different types of severe, extensive dermatitis. Contact sensitization to bronopol in this population is probably facilitated by abnormal cutaneous barrier function. Our findings emphasize the need for further clinical study of the potential for bronopol to produce contact sensitivity, and suggest caution with regard to its use in patients with dermatitis.
The records of eight patients with pyoderma gangrenosum and monoclonal gammopathy showed that all patients except one had an IgA paraproteinemia. To date, seven patients have had a benign course and multiple myeloma has developed in one. In seven patients, the onset of the pyoderma gangrenosum preceded the detection of the monoclonal gammopathy. The monoclonal gammopathy did not seem to influence the morphologic findings, course, or therapy of the pyoderma gangrenosum. In the one patient with myeloma, treatment of the myeloma caused accelerated healing of the skin lesions.
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.
Since 1973, we have identified and collected follow-up data on 16 patients with hypocomplementemic urticarial vasculitis. Preliminary diagnostic criteria are the presence of typical urticarial skin lesions and low levels of serum complement (all components), plus two of the following: dermal venulitis, arthritis, glomerulo-nephritis, episcleritis or uveitis, recurrent abdominal pain, and C1q precipitin in plasma. Exclusions are systemic lupus erythematosus, mixed cryoglobulinemia, elevated antinuclear antibody titer, hereditary deficiency of a complement component or of C1 esterase inhibitor, and presence of anti-native DNA or hepatitis B antigen. The renal involvement is relatively benign, and generally the patients do well and respond to specific treatment when this is indicated. Eight of 10 smokers studied had evidence of chronic obstructive pulmonary disease, 1 of whom died of this complication. In three patients, severe chronic obstructive pulmonary disease developed at a young age after relatively low pack-year cigarette smoking histories. Lung disease probably results from the interaction of two major risk factors-smoking and an immunologically mediated process that has not been identified.
Biopsy specimens of normal skin of 11 patients with primary biliary cirrhosis were studied by immunofluorescence for immunoglobulin and complement deposition. Of the 11 patients, seven had positive immunofluorescent staining, primarily in a granular pattern either at the basement membrane zone or around the blood vessels or in both locations. The principal immunoglobulin noted was IgM, which, in six of the seven patients, was seen at the basement membrane zone or around the vessels (or both). Deposition with C3, fibrin, IgA, and IgG was seen less frequently. In this series of patients, cutaneous lesions included discoid lupus erythematosus, lichen planus, vitiligo, chronic bullous lesions of the legs, and scleroderma. Non-organ-specific immunologic markers in this group included elevated levels of IgG, IgM, and IgA, antinuclear antibodies, anti-nDNA, rheumatoid factor, antimitochondrial antibodies, smooth-muscle antibodies, and circulating immune complexes. We wish to add cutaneous immunofluorescence as an additional immunologic marker for primary biliary cirrhosis.
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Direct immunofluorescent microscopy was positive on skin biopsy specimens in thirty-one of sixty patients with various forms of psoriasis. Patients with positive immunofluorescence were classified into five main clinical subgroups: (1) psoriasis vulgaris with decreased tolerance to sunlight or ultraviolet light B (eight patients), (2) psoriatic arthritis (seven patients), (3) guttate psoriasis (five patients), (4) pustular psoriasis (four patients), and (5) "uncomplicated" psoriasis vulgaris (seven patients). Various patterns of deposition of immunoglobulins, complement, and fibrin were seen in the five subgroups, the most consistent being granular C3 at the basement membrane zone in specimens from five of the seven patients with guttate psoriasis. Direct immunofluorescent microscopy was usually negative in psoriasis vulgaris, but positive results may be anticipated in special forms of psoriasis.
Receptors for C3b in normal skin were studied. C3b was produced by treating normal human serum with cobra venom factor and by partial digestion of purified C3 with trypsin. Cryostat sections of normal human skin were incubated with C3b, followed by a direct immunofluorescent technique using monospecific goat antihuman C3. The histologic localization of C3b fluorescence was ascertained by fixing cryostat sections with glutaraldehyde and staining with hematoxylin and eosin. The following structures showed staining with anti-C3: (1) endothelial cells in capillaries, larger vessels, and arteries, (2) smooth muscle in arrector pilori muscles and artery walls, and (3) myoepithelial cells in the secretory portion of sweat glands. C3b did not bind to the intercellular substance nor to the basement membrane zone in normal human skin. Normal human sera treated with EDTA, EGTA, and heat (56 degrees C for 30 min) were negative, as was purified C3 by itself, thus indicating that native C3 did not bind to these receptors. Specificity for C3/C3b was shown by blocking with both unconjugated rabbit antihuman C3 and purified C3. The endothelial C3b receptor may have an important role in the localization of immune complexes in cutaneous vasculitis.
Direct immunofluorescence microscopic techniques were used to identify immunoglobulins and complement in the oral biopsy specimens of 22 patients with recurrent aphthous stomatitis (RAS). Ten (45%) of 22 patients demonstrated fluorescence along the basement membrane zone, and vascular fluorescence was seen in seven patients. These findings are in agreement with those of previous immunofluorescence microscopic studies of RAS and suggest the possibility that circulating immune complexes may play a role in the tissue damage seen in this disease.