PubMed Health⌕ Search

Biomedical subjects

D Zillikens

Publications and source records attributed to D Zillikens.

At least 19 recordsLinked to original sources
PubMed2006

Improved protocol for treatment of pemphigus vulgaris with protein A immunoadsorption.

BACKGROUND: Pemphigus vulgaris is a life-threatening autoimmune blistering skin disease, usually treated with high-dose corticosteroids in combination with other immunosuppressants. However, this regimen may prove inadequate in severe cases and can cause dangerous side-effects. We have recently reported protein A immunoadsorption (PAIA) to be an effective adjuvant treatment for induction of remission in severe pemphigus. However, in a significant number of cases, the disease rapidly recurred once PAIA and immunosuppressive medication were tapered. AIMS: The aim of the present study was to develop a PAIA-based therapeutic regimen that would result in a more prolonged remission of pemphigus. METHODS: Nine patients with pemphigus vulgaris were treated with a modified protocol characterized by a combination of PAIA with a higher initial dose of systemic methylprednisolone (2 mg/kg). In addition, azathioprine or mycophenolate mofetil was administered as a steroid-sparing agent. RESULTS: In all nine patients treated with this regimen, we observed a sharp decline of circulating autoantibody levels and dramatic improvement of cutaneous and mucosal lesions within 4 weeks of therapy. The patients remained free of clinical disease for up to 26 months after PAIA treatment was discontinued. CONCLUSION: The improved treatment protocol appears to combine highly effective induction of clinical remission in severe or treatment-resistant pemphigus with a prolonged subsequent symptom-free interval.

Aged↗
PubMed2006

Rituximab in refractory autoimmune bullous diseases.

Treatment of autoimmune blistering diseases consists of systemic glucocorticosteroids usually in combination with additional immunosuppressants such as azathioprine and mycophenolate mofetil or immunomodulators such as dapsone, antibiotics, intravenous immunoglobulins, and immunoadsorption. In some patients, these treatment regimens are not sufficient to control disease activity and/or lead to intolerable adverse events. Rituximab, originally developed for the treatment of non-Hodgkin's lymphoma, is an anti-CD20 humanized monoclonal antibody leading to transitory B-cell depletion. For this indication, rituximab is widely employed, and severe side-effects rarely observed. Subsequently, the B-cell-depleting effect of rituximab has been exploited successfully in various autoimmune disorders, including autoimmune blistering diseases. Here, we review the effect of rituximab in such diseases. To date, application of rituximab has been reported in 26 treatment-resistant patients with the vulgaris, foliaceus, and paraneoplastic variants of pemphigus as well as in bullous pemphigoid and epidermolysis bullosa acquisita. All but a single patient showed clinical improvement with reduction of lesion formation. In about a third, a clinical remission requiring further immunsuppressive medication was achieved, and in about a quarter, complete remission was induced. In addition, the mode of action and adverse events of rituximab as well as adjuvant immunosuppressive treatments, and the effect on levels of circulating autoantibodies in these patients are discussed.

Antibodies, Monoclonal↗
PubMed2005

[Successful treatment of subcorneal pustular type of IgA pemphigus].

IgA pemphigus is a rare autoimmune intraepidermal blistering disease characterized by in vivo bound, and circulating IgA autoantibodies that target cell surface components (cadherins) of epidermal keratinocytes. The average age of onset is approximately 50 years. Histological hallmarks of IgA pemphigus are epidermal acantholysis, subcorneal or intraepidermal pustulosis, and neutrophilic infiltration. The main clinical characteristics are erythematous skin lesions with vesiculopustules, erosions, crusts and desquamation, favoring the trunk, groins, auxiliaries, and proximal extremities. The drug of choice for treating IgA pemphigus is diaminodiphenylsulfone. In this case study, we describe a patient who suffered from IgA pemphigus and responded well to diaminodiphenylsulfone.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2005

Successful adjuvant treatment of severe bullous pemphigoid by tryptophan immunoadsorption.

Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with circulating autoantibodies to the hemidesmosomal antigens BP180 and BP230. We report two cases of therapy-refractory BP adjuvantly treated by tryptophan immunoadsorption. In both patients, this treatment was associated with rapid clinical improvement and reduction in the required corticosteroid dosage. In addition, levels of circulating anti-BP180 autoantibodies decreased markedly. Antibodies that were eluted from the tryptophan matrix bound to BP180 and induced dermal-epidermal separation in cryosections of human skin. Our observations suggest that immunoadsorption may be a helpful adjuvant treatment in severe BP.

Adrenal Cortex Hormones↗
PubMed2004

[Differential diagnosis of bullous skin lesions in neonates: pemphigoid gestationis].

The clinical relevance of bullous skin diseases in newborns varies widely. We present the case of a preterm, 35 weeks of gestation, infant who was admitted to our hospital with skin lesions on face, thorax and plantae. There were no other pathological findings on clinical and neurological examinations. During another pregnancy the mother of the child had already suffered from pemphigoid gestationis. In the blood of the newborn complement-fixing auto-antibodies against BP180, the common antigen of pemphigoid gestationis and bullous pemphigoid, were detected. The skin lesions disappeared after a few days of local antiseptic therapy. Pemphigoid gestations is a rare autoimmune dermatosis in pregnancy. The frequency of skin lesions in newborns of mothers with pemphigoid gestationis is estimated to about 5 -- 10 %.

Diagnosis, Differential↗
PubMed2004

Elevated expression and release of tissue-type, but not urokinase-type, plasminogen activator after binding of autoantibodies to bullous pemphigoid antigen 180 in cultured human keratinocytes.

In bullous pemphigoid (BP), the binding of BP180-specific antibodies to their hemidesmosomal target antigen is not sufficient for blister formation, but must be accompanied by the release of proteases. Using plasminogen activator (PA) knock-out mice, the PA system has previously been shown to be a prerequisite for blister formation in experimental murine BP. Here, we found elevated levels of plasmin and tPA, but not of uPA, in blister fluid from BP patients (n = 7) compared to blisters from patients with toxic epidermal necrolysis (n = 4) and suction blisters in healthy controls (n = 7). Subsequently, we addressed the question whether keratinocytes release PA in response to the binding of anti-BP180 antibodies. Treatment of cultured normal human keratinocytes with BP IgG, but not with control IgG, led to both increased protein and mRNA levels of tPA, but not of uPA, as determined by ELISA and RT-PCR, respectively. The specificity of this finding was confirmed using BP180-deficient keratinocytes from a patient with generalized atrophic benign epidermolysis bullosa, where no tPA release was observed after stimulation with BP IgG. Our results show the elevated expression and release of tPA from normal human keratinocytes upon stimulation with antibodies to human BP180. Keratinocytes, by secreting tPA, may thus play an active role in blister formation of BP.

Autoantibodies↗
PubMed2003

[Treatment of lichen planus pemphigoides with acitretin and pulsed corticosteroids].

A patient with lichen planus pemphigoides first developed multiple pruritic papules and subsequently, tense blisters on trunk and extremities. Histopathologic examination of a skin biopsy demonstrated both the typical changes of lichen planus and subepidermal blisters as in bullous pemphigoid. Direct immunofluorescence microscopy revealed both cytoid bodies and linear C3 deposits at the dermal-epidermal junction. By indirect immunofluorescence microscopy on 1 M NaCl-split-skin, circulating autoantibodies labeled the epidermal side of the split. Immunoblot analysis showed binding of the antibodies to the cell-derived soluble 120 kD domain of the 180 kD bullous pemphigoid antigen and to a recombinant form of the immunodominant NC16A region of this protein. When treated with pulsed intravenous corticosteroids, the patient continued to develop new papules and blisters, but when oral acitretin was added, the skin lesions cleared. The immunoblot reactivity of the patient's autoantibodies well reflected disease activity, while the indirect immunofluorescence microscopy titers did not.

Acitretin↗
PubMed2003

Protein A immunoadsorption: a novel and effective adjuvant treatment of severe pemphigus.

BACKGROUND: Pemphigus foliaceus (PF) and pemphigus vulgaris (PV) are autoimmune blistering skin diseases usually treated with high-dose systemic corticosteroids and other immunosuppressants that may cause severe side-effects. Plasmapheresis also has been demonstrated to be of benefit in the treatment of pemphigus. In contrast to plasmapheresis, staphylococcal protein A immunoadsorption (PA-IA) specifically removes immunoglobulin from the circulation, allows treatment of larger plasma volumes, and does not require the substitution of plasma components. OBJECTIVES: To determine the effectiveness and side-effects of PA-IA in patients with severe pemphigus. METHODS: Five patients with severe pemphigus (PV, n = 4; PF, n = 1) were treated by PA-IA. Three of these patients had been refractory to various treatment regimens. In addition to PA-IA, methylprednisolone, 0.5 mg x kg-1 body weight day-1 was given initially and subsequently tapered. RESULTS: In all patients, a dramatic clinical improvement was seen within 2 weeks after initiation of therapy. Patients were free of lesions after 3, 4, 4, 10 and 21 weeks of treatment, respectively. Concurrently, autoantibody levels decreased rapidly. CONCLUSIONS: PA-IA is a rational, effective, and safe adjuvant therapy for severe pemphigus and warrants wider use for this indication. A controlled study should compare side-effects and effectiveness of PA-IA with other treatment options for pemphigus.

Adjuvants, Immunologic↗
PubMed2003

Tufted hair folliculitis associated with pemphigus vulgaris.

Tufted hair folliculitis (THF) is a rare disease which is characterized by the emergence of multiple hairs from widely dilated follicular orifices surrounded by an inflammatory infiltrate resulting in scarring alopecia. The pathogenesis is not yet fully understood. Although colonization with Staphylococcus aureus could not always be detected and systemic treatment with antibiotics alone is not sufficient, this microorganism is considered to play an important role. Around 30 patients with THF have been reported since the first publication. We present a patient with pemphigus vulgaris who developed THF. To our knowledge, this is the fourth case with an association of these two entities. Amongst other causing mechanisms, the autoimmune reaction may play an important role for the development of THF.

Administration, Topical↗
PubMed2002

[Blistering autoimmune diseases of childhood].

Autoimmune blistering skin diseases are exceedingly rare in children. In most cases, they are characterized by circulating autoantibodies directed against adhesion structures of the skin which subsequently induce blistering at the dermoepidermal junction or intraepidermally. The most frequent paediatric immunobullous disease is linear IgA dermatosis; all others such as pemphigoid, epidermolysis bullosa acquisita, dermatitis herpetiformis and pemphigus are less common than in adults. In children, mucous membranes are involved more frequently. Recent advances in the identification of the autoantigens have improved diagnostic approach and therapeutic management of blistering diseases. In most cases, treatment requires systemic immunosuppression. With respect to the chronic course of the diseases and potential complications of treatment, cooperation between dermatologists and paediatricians seems advisable.

Autoimmune Diseases↗