Kristin M. Leiferman

Drug-induced linear IgA bullous dermatosis: report of six cases and review of the literature.

BACKGROUNDnLinear IgA bullous dermatosis (LABD) is an autoimmune subepidermal blistering disease that may be associated with drug exposure.nnnOBJECTIVEnOur purpose was to compare the clinical, pathologic, and immunofluorescence findings in drug-induced LABD with those in the idiopathic type.nnnMETHODSnSix patients with an acute drug eruption were identified who had linear IgA deposition at the basement membrane zone (BMZ). Lesional tissue was examined by brightfield microscopy, and perilesional tissue was examined by direct immunofluorescence (DIF). The presence of circulating BMZ antibody was assayed by indirect immunofluorescence (IIF) on monkey esophagus (ME) and salt-split human skin (SS).nnnRESULTSnHistopathologic examination showed subepidermal bullae with varying numbers of inflammatory cells. DIF showed linear IgA at the BMZ; three of the patients also had weak deposition of C3 at the BMZ. Serum from five patients was studied by IIF. One patient had circulating IgA BMZ antibodies in a titer of 1:80 on ME, localized to the dermal side on SS. All patients were free of lesions within 5 weeks after discontinuation of the drug.nnnCONCLUSIONnDrug-induced LABD is a self-limited eruption characterized by linear deposition of IgA without IgG at the BMZ. Most patients lack circulating antibodies. The distribution of lesions and the course of the disease differ from those of idiopathic LABD.

Follicular mucinosis: Clinical and histopathologic study

Fifty-nine patients with the histologic diagnosis of follicular mucinosis (alopecia mucinosa) were evaluated retrospectively. Thirty-seven were male and 22 were female; ages ranged from 10 to 76 years. Of 19 patients with mycosis fungoides, 16 had initial lesions of follicular mucinosis on the trunk or extremities. Two patients had Hodgkins disease and follicular mucinosis; both were younger than 20 years of age. Seven other patients were 20 years of age or younger. Two of the nine adolescent patients had persistent plaques of follicular mucinosis up to 18 years after diagnosis. Evaluation of biopsy specimens for lymphocytes, eosinophils, nonlymphoid cell infiltration, epidermal lymphocytic exocytosis, mucin deposition, and epidermal hyperplasia revealed no predominant feature that differentiated the group with benign disease from the group with mycosis fungoides. We conclude that no single clinical or histopathologic observation predicts which patients with follicular mucinosis will have a benign course and that evaluation of multiple clinical and histologic variables is necessary.

Eosinophils in atopic dermatitis.

The eosinophilic granulocyte is commonly associated with allergic inflammation. Although blood eosinophilia frequently accompanies atopic dermatitis, accumulation of tissue eosinophils is not prominent. Recent studies have elucidated the structure, content, and activities of the eosinophil. In addition, immunofluorescence localization of eosinophil granulate proteins has shown that eosinophils disrupt in tissue depositing toxic granule proteins in several diseases. Here, evidence for eosinophil degranulation in atopic dermatitis is presented and mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects in atopic dermatitis and related conditions are discussed.

Dermal eosinophils in atopic dermatitis undergo cytolytic degeneration

BACKGROUNDnImmunofluorescent staining for eosinophil granule proteins in lesional skin of patients with atopic dermatitis shows extensive extracellular deposition throughout the upper dermis with relatively few intact eosinophils.nnnOBJECTIVEnThis study was carried out to determine whether eosinophil granule protein deposition in atopic dermatitis occurs by classical exocytosis, by piecemeal degranulation, or as a result of cytolysis.nnnMETHODSnSkin biopsy specimens from 10 patients with atopic dermatitis were examined by electron microscopy.nnnRESULTSnThe biopsy specimens showed varying degrees of dermal eosinophil granule major basic protein deposition by indirect immunofluorescence. Specimens from seven patients showed striking alterations of eosinophils by electron microscopy including intact eosinophils with granule alterations (reversal of core staining and/or core lucency) and with uropod processes. Biopsy specimens from six patients showed evidence of eosinophil degeneration with disruption of nuclear and/or plasma membranes. In four patients specimens, membrane-bound eosinophil granules were present near degenerating eosinophils or were present in the absence of recognizable eosinophils. Evidence of classical exocytotic degranulation was not observed. Two of the specimens were also examined by immunoelectron microscopy for major basic protein localization. In these, major basic protein appeared to be lost from the granule core and distributed in the eosinophil cytoplasm as granules disintegrated and the cell disrupted.nnnCONCLUSIONnThese findings support the hypothesis that eosinophils undergo cytolysis with release of granule contents and membrane-bound granules; this is likely the usual mechanism of eosinophil granule protein release in atopic dermatitis.

A current perspective on the role of eosinophils in dermatologic diseases

Eosinophils are frequently observed in cutaneous inflammation, but little is known of their significance in the pathophysiology of cutaneous disease. Recent studies of the structure, content, and activities of the eosinophil have shown that it has potent toxic proteins with the potential to mediate tissue damage. Furthermore, immunofluorescent localization of eosinophil granule proteins has shown that eosinophils disrupt in tissue and deposit toxic granule proteins. The deposition of granule proteins in several diseases is vastly out proportion to the number of identifiable cells and indicates that eosinophil involvement in cutaneous disease cannot be judged by the number of intact eosinophils in the tissue. Specifically, deposition of eosinophil granule proteins outside of eosinophils has been observed in eczematous lichenified disorders with elevated serum levels of immunoglobulin E, in urticarial and angioedematous disorders, and in bullous diseases. The structural, compositional, and functional characteristics of eosinophils are reviewed, and evidence of eosinophil degranulation in cutaneous diseases is presented. Mechanisms whereby eosinophil degranulation may mediate pathophysiologic effects are also discussed.

Bullous morphea: Clinical, pathologic, and immunopathologic evaluation of thirteen cases

BACKGROUNDnBullous morphea is a rare disease. Its pathogenesis is unknown.nnnOBJECTIVEnWe evaluated bullous morphea clinically, pathologically, and immunopathologically and investigated the role of spirochetes and eosinophils in its pathogenesis.nnnMETHODSnThe clinical and pathologic findings from 13 patients with bullous morphea were reviewed. Tissue sections were studied with the Elias-Bosma stain for spirochetes and indirect immunofluorescence for eosinophil granule major basic protein.nnnRESULTSnBullae were found in all forms of morphea; the lower extremities were the most common sites of involvement. Lymphatic dilatation was found in 77% of the patients. Deposition of major basic protein was found in 60% of cases studied. There was no evidence of spirochetes in any of the specimens examined with the Elias-Bosma stain.nnnCONCLUSIONnOur results suggest that the pathogenesis of bullous morphea is related to lymphatic dilatation as well as release of major basic protein from eosinophils in some patients. We found no association between spirochetes and bullous morphea.

Familial eosinophilic cellulitis, dysmorphic habitus, and mental retardation

BACKGROUNDnEosinophilic cellulitis is a polymorphous, chronic disease characterized by eosinophil infiltration and granulomatous inflammation.nnnOBJECTIVEnOur purpose was to describe the clinical, histologic, and immunohistologic findings in three family members who have had eosinophilic cellulitis since childhood associated with mental retardation and abnormal body habitus.nnnMETHODSnFamily members were evaluated. Multiple skin biopsy specimens were obtained and examined after hematoxylin-and-eosin staining, by immunofluorescence and by electron microscopy. Blood specimens were analyzed by immunoassays for eosinophil granule proteins and eosinophil active cytokines.nnnRESULTSnThree short-statured, mentally retarded family members with abnormal body habitus in at least two generations had recurrent eosinophilic cellulitis. Peripheral blood and bone marrow eosinophilia was present. Plasma eosinophil granule major basic protein and eosinophil-derived neurotoxin levels were elevated with normal plasma eosinophil cationic protein levels. Eosinophil survival in culture was increased by patients plasma and was blocked with monoclonal interleukin-5 antibody. The level of plasma interleukin-5 was elevated. Lesional skin biopsy specimens showed massive staining for three eosinophil granule proteins. Electron microscopy showed eosinophil disruption.nnnCONCLUSIONnEosinophilic cellulitis, mental retardation, and abnormal body habitus were likely inherited as a dominant syndrome in this family in which eosinophil involvement was striking.

Episodic angioedema with eosinophilia.

A 40-year-old woman had monthly episodes of angioedema, eruption of pruritic papules and plaques and fever. During acute episodes white blood cell counts increased to 31,000/mm3 with 75% eosinophils, body weight increased to 10% of baseline weight, and urine excretion decreased to 40 ml/24 hours. No evidence was found for cardiac or other visceral organ involvement. Extensive diagnostic evaluations revealed no evidence for parasitic infestation, connective tissue disease, or neoplastic disorders. Results of immunologic studies revealed increased serum IgM and IgE levels and showed elevated levels of circulating activated T-helper cells. Biopsy specimens of lesional skin showed dermal infiltration of lymphocytes and eosinophils with deposition of eosinophil granule major basic protein in the extracellular matrix within the dermis. Immunophenotyping of the dermal infiltrate with monoclonal antibodies revealed the predominance of T-helper cells, many of them expressing the human leukocyte antigen (HLA)-DR, suggesting that angioedema with eosinophilia may be a T-helper cell-mediated disease.