Search PubMed⌕ Search

Biomedical subjects

D Zillikens

Publications and source records attributed to D Zillikens.

At least 91 records · Page 5Linked to original sources
PubMed1996

A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone.

Several components of the basement membrane zone (BMZ) have been identified as antigenic targets in autoimmune bullous diseases. We report a novel disease with autoantibodies to a BMZ antigen that is different from the targets described so far. The patient suffering from this disorder showed tense bullae and severe mucous membrane involvement rapidly responding to oral tetracyclines and colchicine. Histopathologic findings resembled those of dermatitis herpetiformis. Direct immunofluorescence microscopy showed linear deposits of IgG and C3 at the BMZ. By indirect immunofluorescence studies on split human skin, using both 1 M NaCl and suction blistering for dermal-epidermal separation, IgG antibodies localized exclusively to the dermal side of the split. The antibodies were mainly of the IgG4 sub-class. By Western blot analysis of epidermal and dermal extracts, the patient's serum unequivocally reacted with a dermal antigen of 200 kDa. It did not recognize bullous pemphigoid antigens (the autoantigen of epidermolysis bullosa acquisita), purified preparations of laminin-1 and laminin-5, or the recently described 105-kDa BMZ antigen. By immunoblotting of concentrated conditioned SCC-25 medium, the patient's antibodies reacted with a band of 200 kDa and several bands of lower molecular weight. No reactivity was seen with extracts of cultured human fibroblasts. By indirect immunogold electron microscopy, immunoreactants localized to the lower lamina lucida. After clearance of skin lesions, both indirect immunofluorescence and Western blot analysis became negative. This patient suffers from a novel autoimmune bullous disease with autoantibodies to a 200-kDa antigen of the BMZ.

Animals↗
PubMed1996

A novel subepidermal blistering disease with autoantibodies to a 200-kDa antigen of the basement membrane zone.

Several components of the basement membrane zone (BMZ) have been identified as antigenic targets in autoimmune bullous diseases. We report a novel disease with autoantibodies to a BMZ antigen that is different from the targets described so far. The patient suffering from this disorder showed tense bullae and severe mucous membrane involvement rapidly responding to oral tetracyclines and colchicine. Histopathologic findings resembled those of dermatitis herpetiformis. Direct immunofluorescence microscopy showed linear deposits of IgG and C3 at the BMZ. By indirect immunofluorescence studies on split human skin, using both 1 M NaCl and suction blistering for dermal-epidermal separation, IgG antibodies localized exclusively to the dermal side of the split. The antibodies were mainly of the IgG4 subclass. By Western blot analysis of epidermal and dermal extracts, the patient's serum unequivocally reacted with a dermal antigen of 200 kDa. It did not recognize bullous pemphigoid antigens, the autoantigen of epidermolysis bullosa acquisita, purified preparations of laminin-1 and laminin-5, or the recently described 105-kDa BMZ antigen. By immunoblotting of concentrated conditioned SCC-25 medium, the patient's antibodies reacted with a band of 200 kDa and several hands of lower molecular weight. No reactivity was seen with extracts of cultured human fibroblasts. By indirect immunogold electron microscopy, immunoreactants localized to the lower lamina lucida. After clearance of skin lesions, both indirect immunofluorescence and Western blot analysis became negative. This patient suffers from a novel autoimmune bullous disease with autoantibodies to a 200-kDa antigen of the BMZ.

Autoantibodies↗
PubMed1996

High-titer interferon-alpha antibodies in a patient with pemphigus foliaceus.

Among 13 patients with pemphigus or bullous pemphigoid, high titers of anti-interferon-alpha (IFN-alpha) antibodies were present in all serum samples of one patient suffering from pemphigus foliaceus. This patient was characterized by a relatively benign course of the disease. The IFN antibodies were of oligoclonal or polyclonal origin, predominantly of the IgG subtype, and displayed a broad spectrum of specificity including various natural and recombinant IFN-alpha subtypes as well as recombinant IFN-omega 1. In vitro, these antibodies neutralized both the antiviral and antiproliferative activities of the respective IFN types. Recognition of the patient's endogenous IFN-alpha demonstrated their autoantibody nature. The IFN antibodies were present at diagnosis and resistant to continued immunosuppressive treatment. Despite clinical remission, the IFN antibodies persisted, suggesting that they were not pathogenically related to the skin manifestations of the pemphigus. There were no sings of immune complex-mediated organ damage. IFN antibodies constitute a new class of autoantibodies that may occur in conjunction with pemphigus and likely interfere with the endogenous IFN system.

Adult↗
PubMed1996

Scalp necrosis in temporal (giant cell) arteritis:implications for the dermatologic surgeon.

Temporal arteritis, a variant of giant cell arteritis, is a systemic granulomatous vasculitis of large and medium-sized arteries. Usually the clinical features are dominated by ophthalmological and neurological complications. In rare instances, ischaemic necrosis, especially of the scalp, may lead patients to the dermatologist. We report a 76-year-old woman presenting with a unilateral scalp necrosis, accompanied by a dramatic ipsilateral impairment of vision. Immediately after duplex-sonography of the extracranial vessels and after initiation of corticosteroid therapy, the diagnosis of temporal arteritis was confirmed by temporal artery biopsy. One month later, because of insufficient secondary healing of the ulcer, the defect was covered by a mesh graft. The taking of the graft was delayed due to immunosuppressive therapy, but was complete. The patient unfortunately died as a result of complications related to surgical removal of an aspergilloma in the sphenoid cavity secondary to immunosuppressive therapy. We discuss the technique of artery biopsy and the possibility of surgical management of scalp necrosis in temporal arteritis.

Aged↗
PubMed1995

[Herpes gestationis. Clinical spectrum and diagnostic possibilities].

Herpes gestationis (HG) is a rare autoimmune disease of pregnancy. We report on five patients in whom the clinical diagnosis was confirmed by histology, immunofluorescence and immunoblot studies. The time of onset ranged from the 8th week of pregnancy to the 1st day post partum. In one patient erosions and ulcerations of the oral cavity predominated while the remainder of the skin was nearly unaffected. One patient had intense pruritus without any skin eruptions during the final 8 weeks of her pregnancy, developing bullous lesions on the 1st day post partum. The other patients initially suffered from pruritic polymorphic skin lesions, followed by vesiculae and bullae. In the serum of all patients, the complement-fixing HG factor was found. Immunoblot studies with epidermal and dermal extracts demonstrated the binding of the antibodies to a 180-kD protein of the epidermis. All patients improved markedly with medium dosages of systemic corticosteroids. In four cases the newborns were healthy and mature, and in one case, the infant met all criteria for a "small-for-dates" baby. We discuss both clinical spectrum and diagnostic options of HG and review new aspects related to the pathogenesis of this disease.

Adult↗
PubMed1995

[Cicatricial pemphigoid--a therapeutic problem].

Cicatricial pemphigoid is an autoimmune subepidermal blistering disease of the skin and mucous membranes. We report on eight patients in whom the clinical diagnosis was confirmed by direct immunofluorescence. The patients' age averaged 69 years; seven were female and one male. Initial symptoms were erosions of the oral mucous membranes in four patients, skin blisters in three patients, and in one patient an ocular involvement was the first manifestation of the disease. Indirect immunofluorescence on NaCl-split human skin revealed circulating IgG antibodies binding to the roof of the artificial blister in three patients. Immunoblotting of epidermal and dermal extracts disclosed binding of IgG antibodies of one of these patients to an epidermal 230-kD protein, whereas IgA-antibodies showed no specific binding. In four of five patients with a strong ocular involvement IgA deposits were found by direct immunofluorescence. These studies were done on biopsies of perilesional skin or oral mucous membranes, and they were positive in one patient even before the first ocular lesions appeared. Therefore, finding of IgA deposits by direct immunofluorescence may be taken as a prognostic criterion allowing selection of the proper treatment. We treated six patients with a dexamethasone-cyclophosphamide pulse therapy, while two patients received dapsone orally. The involvement of skin and oral mucous membrane responded well to both regimens, whereas the ocular lesions were progressive, except in one patient. On the basis of our eight cases, we discuss both options and limitations in the treatment of cicatricial pemphigoid and review new aspects of the pathogenesis of this disease.

Aged↗
PubMed1995

[Bullous pemphigoid simulation subacute simple prurigo].

Bullous pemphigoid (BP) is a bullous autoimmune disease of the elderly; it is characterized by tense bullae on both erythematous and otherwise apparently normal skin. Several clinical variants of BP have been described, and we now add our observations of two BP cases mimicking subacute prurigo. Both patients had suffered from intensely pruritic excoriated papules for several months before presentation. Blisters had never developed and did not occur during follow up. Histology showed changes of chronic dermatitis. In the serum of both patients, indirect immunofluorescence on NaCl-separated human skin revealed the presence of circulating antibodies binding to the roof of the artificial blisters. Perilesional skin biopsies showed linear IgG or C3-deposits in the basement membrane zone. Immunoblotting of epidermal and dermal extracts demonstrated the binding of the antibodies to an epidermal 230-kD protein, which is the known major bullous pemphigoid antigen. These cases are described as a basis for discussion of the clinical spectrum of bullous pemphigoid.

Acute Disease↗
PubMed1994

Influence of various cytokines on the interleukin-2-dependent lysis of melanoma cells in vitro.

To obtain information about useful combinations of various cytokines in melanoma therapy, we studied the influence of interleukin-2 (IL-2) in combination with interferon-alpha (IFN-alpha), IFN-gamma and tumour necrosis factor-alpha (TNF-alpha) on the lytic activity of IL-2-stimulated cells in vitro. Peripheral mononuclear cells (PMC) were incubated for 4 days with various combinations of cytokines and used as effector cells. Two different melanoma cell lines (M19 and M26) were used as target cells. The lytic activity of stimulated PMC was determined using a modified hexosaminidase assay. IL-2 was mainly responsible for the lytic activity of the effector cells in a dose-dependent manner. IFN-alpha, IFN-gamma and TNF-alpha did not enhance lytic activity with an optimal IL-2 dose (50 IU/ml IL-2). Using a suboptimal IL-2 dose (5 IU/ml), they increased cytotoxicity. The specific lysis of M19 cells was significantly increased by pretreatment of the cells with 5 IU/ml IFN-alpha together with 50 IU/ml TNF-alpha (t-test, P < or = 0.001), while the specific lysis of M26 cells was increased by pretreatment with 5 IU/ml IFN-gamma. We conclude that the lysis of melanoma cells by cytotoxic cells in vitro can be enhanced by various cytokines. The optimal cytokine combination differed for the two melanoma cell lines tested.

Cytokines↗
PubMed1994

[Inflammatory type of epidermolysis bullosa acquisita].

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease, which can present in various clinical forms. We report on a 73-year-old male patient with the inflammatory type of EBA, which is clinically similar to bullous pemphigoid. Histological examination revealed subepidermal blister formation, and direct immunofluorescence of perilesional skin revealed a linear deposition of IgG and C3 at the basement membrane. Indirect immunofluorescence with 0.9% NaCl-separated human skin as substrate showed the presence of circulating antibodies binding to the base of the artificial blister at a titre of 1:320. Indirect immunoelectronmicroscopy revealed immune deposits localized in the area of the sublamina densa. Immunoblotting of dermal extracts disclosed binding of serum antibodies to a 290-kDa protein. Systemic therapy with diaminodiphenyl sulphone, initially in combination with corticosteroids, resulted in complete healing of the skin lesions. With reference to this case report, we discuss the clinical pictures possible in EBA, the differential diagnosis and the treatment options.

Aged↗
PubMed1994

[Paraneoplastic pemphigus. Induction of autoantibodies against structural proteins in the skin].

Paraneoplastic pemphigus (PP) is a newly reported autoimmune disease, which is always associated with an underlying neoplasia. It is characterized by painful mucosal erosions and ulcerations, and by polymorphous skin lesions reminiscent of erythema multiforme, pemphigus vulgaris and lichen planus pemphigoides. These patients have autoantibodies that bind to a distinct complex of epidermal proteins, including desmoplakin I (250 kD), major bullous pemphigoid antigen (230 kD), desmoplakin II (210 kD) and a 190-kD and a 170-kD protein, neither of which has yet been further characterized. Histological findings include acantholysis, epidermal cell necrosis, vacuolar interface changes and, sometimes, lichenoid infiltrates of the upper dermis. Direct immunofluorescence shows an intercellular deposition of immunoreactants in the epidermis and granular deposits at the dermal-epidermal junction. Indirect immunofluorescence with rodent bladder as substrate shows an intercellular pattern. This method is the most convenient and cost-effective method of screening for PP, since antigens of both pemphigus vulgaris and pemphigus foliaceus are not expressed in this tissue.

Adolescent↗
PubMed1993

Evidence for cell-mediated immune mechanisms in the pathology of pemphigus.

Pemphigus is an autoimmune blistering disease in which autoantibodies have clearly been shown to be pathogenic. Because autoantibodies are also found in uninvolved skin, further mechanisms may be important in the development of pemphigus lesions. In addition to granulocytes, mononuclear cells are commonly found in pemphigus lesions. To elucidate the role of mononuclear cells in the pathology of this disease, we determined the levels of soluble interleukin-2 receptor in blister fluid and serum samples from pemphigus patients prior to treatment. The interleukin-2 receptor (IL-2R) is expressed on activated mononuclear cells. Depending on its rate of synthesis, a portion is released from the cell surface in a soluble form (sIL-2R). In blister fluid, sIL-2R levels were 2186 +/- 288 U/ml (+/- SD), which was significantly higher than levels in concurrently obtained serum samples (1299 +/- 165 U/ml; P < 0.001). In suction blisters in volunteers, and in patients with second-degree burns or friction-induced bullae, sIL-2R levels were normal in both blister fluid and serum. In pemphigus patients, sIL-2R serum levels continuously declined during systemic therapy, correlating with disease activity. Immunohistological studies demonstrated a marked increase in IL-2R+ cells in both the epidermis and dermis of lesional skin compared with perilesional skin. In the dermis, CD3+ T cells predominated, whereas monocytes/macrophages were most frequent in the epidermis. In pemphigus vulgaris, monocytes/macrophages were restricted to the basal keratinocytes, whereas in pemphigus foliaceus, they were found throughout the lesional epidermis. Our data indicate that activated mononuclear cells are present in lesional skin of pemphigus patients, and may contribute to the pathology of this disease.

Aged↗
PubMed1993

[Soluble interleukin 2 receptor as activity parameter in serum of systemic and discoid lupus erythematosus].

The evaluation of disease activity in systemic lupus erythematosus (SLE) is important for selection of the appropriate therapeutic regimen. In addition to the clinical picture, various laboratory parameters are taken into account. However, no validated criteria for the evaluation of the disease activity in SLE have yet been established. Recently, serum levels of soluble interleukin-2 receptor (sIL-2R) have been proposed as a potential parameter for disease activity in SLE. However, the studies reported on this subject so far have focused mainly on certain subsets of the disease, and the evaluation of the disease activity was based on a very limited number of parameters. In the present study, we determined serum levels of sIL-2R in 23 patients with SLE and 30 patients with discoid LE (DLE). Evaluation of disease activity in SLE was based on a comprehensive scale which considered numerous clinical signs and laboratory parameters. In SLE, serum levels of sIL-2R showed a better correlation with disease activity than all the other parameters investigated, including proteinuria, erythrocyte sedimentation rate, serum globulin concentration, titre of antibodies against double-stranded DNA, serum albumin concentration, serum complement levels and white blood cell count. For the first time, we report on elevated serum levels of sIL-2R in DLE, which also correlated with disease activity.

Adolescent↗