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M Goebeler

Publications and source records attributed to M Goebeler.

At least 19 recordsLinked to original sources
PubMed2007

Rituximab in autoimmune bullous diseases: mixed responses and adverse effects.

BACKGROUND: Intolerably high doses of systemic corticosteroids and additional immunosuppressants may be required to control disease activity in autoimmune bullous skin diseases. New therapeutic options are needed for such patients. OBJECTIVES: To determine the efficacy and adverse effects of adjuvant rituximab. METHODS: Seven patients with refractory autoimmune blistering diseases (pemphigus vulgaris, PV, n = 4; bullous pemphigoid, BP, n = 2; mucous membrane pemphigoid, MMP, n = 1) were treated four times with rituximab at an individual dose of 375 mg m(-2) at weekly intervals. RESULTS: All lesions cleared in three patients (two PV, one BP), while they were reduced by more than 50% in three others (two PV, one BP). The concomitant immunosuppressive medication was reduced in five patients (four PV, one BP). The patient with MMP developed bilateral blindness while nasopharyngeal lesions resolved. Three patients (two BP, one PV) experienced severe adverse events including fatal pneumonia. CONCLUSIONS: Adjuvant B-cell depletion by rituximab is effective in otherwise therapy-resistant bullous autoimmune disorders but may be associated with substantial adverse effects including fatal outcomes.

Adolescent↗
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

[Dyskeratosis congenita in a 40-year-old patient].

A 40-year-old patient with a 3-year history of thrombocytopenia was admitted with reticulated and speckled hyper- and hypopigmentations especially on the upper trunk. Aplasia or dystrophy of the fingernails and toenails as well as atresia of the lacrimal ducts were noted. Examination of the oropharynx revealed multiple mucosal leukoplakias and loss of almost all teeth. Based on these observations the diagnosis of X-linked dyskeratosis congenita (Zinsser-Cole-Engman syndrome, OMIM #305000) was made and confirmed by sequencing of the dyskerin 1 (DKC1) gene which revealed a missense mutation in exon 11.

Adult↗
PubMed2006

Elevated serum levels of calcium-binding S100 proteins A8 and A9 reflect disease activity and abnormal differentiation of keratinocytes in psoriasis.

BACKGROUND: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. OBJECTIVES: We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. METHODS: Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. RESULTS: A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of <15 showed serum levels of 705+/-120 ng mL-1 (mean+/-SEM, n=18), those with a PASI of >or=15 showed levels of 1315+/-150 ng mL-1 (n=32) while controls presented with 365+/-50 ng mL-1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional, nonpsoriatic interfollicular epidermis. CONCLUSIONS: Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions.

Acute Disease↗
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↗
PubMed2004

Treatment of recalcitrant pustular psoriasis with infliximab: effective reduction of chemokine expression.

Tumour necrosis factor (TNF)-alpha is thought to play a major role in the pathophysiology of psoriasis. Good clinical responses of psoriasis to anti-TNF-alpha-based therapies have recently been demonstrated. We studied the effect of infliximab, a monoclonal antibody against TNF-alpha, on chemokine expression in pustular psoriasis. A 61-year-old man with a 2-year history of severe pustular psoriasis of von Zumbusch type who did not respond to conventional therapies responded rapidly to treatment with infliximab. The clinical response was reflected by an immediate and effective reduction of the neutrophil-attractant chemokines interleukin (IL)-8 and growth-related oncogene (Gro)-alpha as well as of monocyte chemoattractant protein (MCP)-1, as determined by mRNA in situ hybridization of lesional skin. No expression before or after treatment was seen for monokine induced by interferon (IFN)-gamma (MIG) and IFN-inducible protein (IP)-10. Thus, in pustular psoriasis the chemokine expression pattern is dominated by neutrophil-attractant chemokines and MCP-1 while, in contrast to plaque psoriasis, IFN-gamma-inducible lymphocyte-attractant chemokines such as IP-10 and MIG are not abundant. We conclude that anti-TNF-alpha treatment with infliximab is an effective therapy in severe pustular psoriasis which is reflected by downregulation of disease-promoting chemokines such as IL-8, Gro-alpha and MCP-1.

Antibodies, Monoclonal↗
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

Calcitriol vs. dithranol in combination with narrow-band ultraviolet B (311 nm) in psoriasis.

BACKGROUND: Narrow-band ultraviolet (UV) B (311 nm) phototherapy is an effective treatment for psoriasis. In order to reduce cumulative UV doses and to enhance clearance of psoriasis plaques, combination therapies with topical agents such as dithranol and calcipotriol have been established. OBJECTIVES: To compare the clinical efficacy, in a half-side manner, of UVB (311 nm) in combination with either calcitriol or dithranol. METHODS: Ten patients with symmetrical stable plaque psoriasis were treated with narrow-band UVB (311 nm) five times a week. In addition, topical calcitriol was applied twice daily to one arm, whereas the other arm and the rest of the body were treated once daily with dithranol. The follow-up period was at least 4 weeks. Efficacy was assessed separately for both arms prior to treatment and once weekly thereafter by a modified Psoriasis Area and Severity Index (PASI) score. The cumulative irradiation dose and the number of treatment sessions required for clearance of psoriasis lesions were determined for each patient. Additionally, all patients completed a quality of life questionnaire. RESULTS: Both treatment modalities notably reduced the PASI score. A clinical comparison of UVB (311 nm) in combination with either calcitriol or dithranol revealed no significant therapeutic differences between the regimens. CONCLUSIONS: Combination of narrow-band UVB (311 nm) therapy with calcitriol is equally effective as the combination with dithranol for the treatment of psoriasis. However, patients preferred calcitriol rather than dithranol when both quality of life and treatment acceptability were assessed.

Administration, Topical↗
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↗