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Biomedical subjects

G Kirtschig

Publications and source records attributed to G Kirtschig.

At least 19 recordsLinked to original sources
PubMed2006

Autologous full-thickness skin substitute for healing chronic wounds.

BACKGROUND: Chronic wounds represent a major problem to our society. Therefore, advanced wound-healing strategies for the treatment of these wounds are expanding into the field of tissue engineering. OBJECTIVES: To develop a novel tissue-engineered, autologous, full-thickness skin substitute of entirely human origin and to determine its ability to heal chronic wounds. METHODS: Skin substitutes (fully differentiated epidermis on fibroblast-populated human dermis) were constructed from 3-mm punch biopsies isolated from patients to be treated. Acellular allodermis was used as a dermal matrix. After a prior 5-day vacuum-assisted closure therapy to prepare the wound bed, skin substitutes were applied in a simple one-step surgical procedure to 19 long-standing recalcitrant leg ulcers (14 patients; ulcer duration 0.5-50 years). RESULTS: The success rate in culturing biopsies was 97%. The skin substitute visibly resembled an autograft. Eleven of the 19 ulcers (size 1-10 cm2) healed within 8 weeks after a single application of the skin substitute. The other eight larger (60-150 cm2) and/or complicated ulcers healed completely (n = 5) or continued to decrease substantially in size (n = 3) after the 8-week follow-up period. Wound healing occurred by direct take of the skin substitute (n = 12) and/or stimulation of granulation tissue/epithelialization (n = 7). Skin substitutes were very well tolerated and pain relief was immediate after application. CONCLUSIONS: Application of this novel skin substitute provides a promising new therapy for healing chronic wounds resistant to conventional therapies.

Adult↗
PubMed2005

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune bullous disease in the West. Oral steroids are considered the standard treatment. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH STRATEGY: We searched the Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE to March 2003 and bibliographies from identified studies. SELECTION CRITERIA: Randomised controlled trials of treatments for patients with immunofluorescence confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the studies in terms of the inclusion criteria, five extracted data independently; disagreements were resolved by discussion. Statistical pooling of the data was inappropriate because of heterogeneity of treatments. MAIN RESULTS: We found seven randomised controlled trials with a total of 634 patients. All studies involved different comparisons, none included a placebo group. Different doses, different formulations of corticosteroids and the addition of azathioprine failed to show significant differences in measures of disease control. However, patients who took azathioprine were able to almost halve the amount of prednisone required for disease control. Plasma exchange plus prednisone achieved significantly better disease control than prednisone alone; this favourable effect was not apparent in another study. The latter study also compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality, although total adverse events at six months almost reached statistical significance in favour of plasma exchange plus prednisone. Comparing tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was shown. A very potent topical corticosteroid was compared to oral prednisone in patients with moderate and extensive disease. In patients with extensive disease, the topical steroid group showed significantly better survival and disease control, and less severe complications, while no significant differences for these outcomes were seen in patients with moderate disease. Most of the reported deaths were in patients taking high doses of oral corticosteroids. AUTHORS' CONCLUSIONS: Very potent topical steroids are effective and safe treatments for bullous pemphigoid; their use in extensive disease may be limited by side effects and practical factors. Starting doses of prednisolone greater than 0.75 mg/kg/day do not seem to give additional benefit, lower doses may be adequate for disease control; this could reduce the incidence and severity of adverse reactions. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide may be useful; this needs further validation.

Azathioprine↗
PubMed2005

Erosive lichen planus of the vulva: weak circulating basement membrane zone antibodies are present.

The objective of this study was to investigate whether circulating basement membrane zone (BMZ) antibodies are present in erosive lichen planus (LP) of the vulva. In total, 56 consecutive women with biopsy-confirmed erosive LP of the vulva were recruited from a vulval clinic in a district general hospital and teaching hospital in Oxfordshire. Indirect immunofluorescence (IgG and IgA) was performed on 56 sera, and 15 were tested to IgG subclasses (1-4). Immunoblotting was carried out on salt-split and urea-extracted epidermal skin extracts on 11. The main outcome measure was the presence or absence of staining at the BMZ. Of the 56 sera, 34 (61%) had weak (neat or 1 : 5) epidermal-binding BMZ antibodies (25 had IgG, 5 had IgA, 4 had both IgG and IgA). All 15 sera tested to IgG showed epidermal binding to one or more IgG subclasses: IgG1 (7 sera), IgG2 (7), IgG3 (7) and IgG4 (0). Immunoblotting identified IgG antibodies to bullous pemphigoid (BP)180 (10/11) and BP230 (2/11). The majority (61%) of patients with vulval erosive LP had circulating serum IgG BMZ antibodies, chiefly reacting with BP180. There was subclass restriction of the IgG response to IgG1, 2 and 3. The significance of these antibodies is uncertain, but they may be a marker for the disease.

Adult↗
PubMed2005

Mucosal vulval lichen planus: outcome, clinical and laboratory features.

BACKGROUND: Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas. OBJECTIVE: To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features. SUBJECTS AND METHODS: Forty-four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected. RESULTS: Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC. CONCLUSIONS: Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long-term follow-up, and that all non-healing ulcerative and papular lesions should be biopsied.

Adrenal Cortex Hormones↗
PubMed2004

No association between hepatitis B or C viruses and vulval lichen planus in a UK population.

The aim of the study was to investigate the prevalence of hepatitis C (HCV) antibodies, hepatitis B surface antigen (HBsAg) carriage and liver disease in 100 females with genital lichen planus (LP) in Oxfordshire. Sera were screened for HCV antibodies (AxSYM HCV 3.0 Abbott), HBV surface antigen (AxSYM HBsAg V2 Abbott), mitochrondrial and anti-smooth muscle antibodies. Liver function tests were undertaken. All sera were negative for HCV antibody and HBsAg. Transiently abnormal liver function tests (2) and liver specific antibodies (2) were detected in four patients with no underlying liver disease. We found no association between HBV or HCV and genital LP in this population.

Adult↗
PubMed2003

Interventions for bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune bullous disease in the West. Oral steroids are considered the standard treatment. OBJECTIVES: To assess the effects of treatments for bullous pemphigoid. SEARCH STRATEGY: We searched the Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE to March 2003 and bibliographies from identified studies. SELECTION CRITERIA: Randomised controlled trials of treatments for patients with immunofluorescence confirmed bullous pemphigoid. DATA COLLECTION AND ANALYSIS: Two reviewers evaluated the studies in terms of the inclusion criteria, five extracted data independently; disagreements were resolved by discussion. Statistical pooling of the data was inappropriate because of heterogeneity of treatments. MAIN RESULTS: We found seven randomised controlled trials with a total of 634 patients. All studies involved different comparisons, none included a placebo group. Different doses, different formulations of corticosteroids and the addition of azathioprine failed to show significant differences in measures of disease control. However, patients who took azathioprine were able to almost halve the amount of prednisone required for disease control. Plasma exchange plus prednisone achieved significantly better disease control than prednisone alone; this favourable effect was not apparent in another study. The latter study also compared plasma exchange or azathioprine plus prednisone, but failed to show significant differences for disease control or mortality, although total adverse events at six months almost reached statistical significance in favour of plasma exchange plus prednisone. Comparing tetracycline plus nicotinamide with prednisolone, no significant difference for disease response was shown. A very potent topical corticosteroid was compared to oral prednisone in patients with moderate and extensive disease. In patients with extensive disease, the topical steroid group showed significantly better survival and disease control, and less severe complications, while no significant differences for these outcomes were seen in patients with moderate disease. Most of the reported deaths were in patients taking high doses of oral corticosteroids. REVIEWER'S CONCLUSIONS: Very potent topical steroids are effective and safe treatments for bullous pemphigoid; their use in extensive disease may be limited by side effects and practical factors. Starting doses of prednisolone greater than 0.75 mg/kg/day do not seem to give additional benefit, lower doses may be adequate for disease control; this could reduce the incidence and severity of adverse reactions. The effectiveness of the addition of plasma exchange or azathioprine to corticosteroids has not been established. Combination treatment with tetracycline and nicotinamide may be useful; this needs further validation.

Azathioprine↗
PubMed2003

Interventions for mucous membrane pemphigoid and epidermolysis bullosa acquisita.

BACKGROUND: Mucous membrane pemphigoid and epidermolysis bullosa acquisita are acquired autoimmune blistering diseases of the skin. Although they are rare, both can result in scarring of mucous membranes, which may lead to blindness and life threatening respiratory complications. OBJECTIVES: To assess the effects of treatments for mucous membrane pemphigoid and epidermolysis bullosa acquisita. SEARCH STRATEGY: Randomised Controlled Trials (RCTs) of patients with MMP or EBA were identified from MEDLINE and EMBASE from their inception to March 2000. The Cochrane Skin Group Specialised Register and the Cochrane Controlled Trials Register (CCTR) were last examined in February 2002. The bibliographies from identified studies were searched. The author who has conducted clinical trials in the field was contacted to identify unpublished trials. SELECTION CRITERIA: RCTs involving participants of any ages, and with a diagnosis confirmed by immunofluorescence. Where no RCTs were located, studies with other designs were considered. DATA COLLECTION AND ANALYSIS: Data were extracted from all included studies using a defined electronic data extraction protocol. Two reviewers evaluated the studies in terms of the inclusion criteria. The data from identified RCTs was extracted independently by three reviewers and subsequently checked for discrepancies. Any disagreements were resolved by discussion with each other and the fourth reviewer. Meta-analysis was not appropriate due to a lack of data. MAIN RESULTS: We found two small RCTs of MMP, both conducted in patients with severe eye involvement. The same author conducted both trials. In the first trial cyclophosphamide was superior to prednisone after six months of treatment; all 12 patients responded well to cyclophosphamide versus a good response in only five of 12 patients treated with prednisone (relative risk 2.40, 95% confidence interval 1.23 to 4.69). In the second trial all 20 patients treated with cyclophosphamide responded well to it after three months of treatment, but only 14 of 20 patients responded to the treatment with dapsone (relative risk 1.4, 95% confidence interval 1.07 to 1.90). We were not able to identify a RCT of therapeutic interventions in EBA. Thirty reports of uncontrolled studies of treatment for MMP involving five or more patients and 11 reports of treatment for EBA involving two or more patients were found, but were difficult to interpret. REVIEWER'S CONCLUSIONS: There is limited evidence (from two small trials) that severe ocular mucous membrane pemphigoid responds best to treatment with cyclophosphamide combined with corticosteroids, and that mild to moderate disease in most patients seems effectively suppressed by treatment with dapsone. It is difficult to make any treatment recommendations for EBA in the absence of reliable evidence sources.

Cyclophosphamide↗
PubMed2002

Guidelines for the management of bullous pemphigoid.

These guidelines have been prepared for dermatologists on behalf of the British Association of Dermatologists. They present evidence-based guidance for treatment, with identification of the strength of evidence available at the time of preparation of the guidelines and a brief overview of epidemiological aspects, diagnosis and investigation. The guidelines reflect data available from Medline, Embase, the Cochrane library, literature searches and the experience of the authors of managing patients with bullous pemphigoid in special and general clinics for over 10 years. However, caution should be exercised in interpreting the data obtained from the literature because only six randomized controlled trials are available involving small groups of patients.

Administration, Topical↗
PubMed2002

Follicular and epidermal alterations in patients treated with ZD1839 (Iressa), an inhibitor of the epidermal growth factor receptor.

We report the cutaneous side-effects of ZD1839 (Iressa), a new anticancer agent that acts by inhibiting epidermal growth factor (EGF) receptor signal transduction. Three patients receiving ZD1839 developed an eruption consisting of follicular papules and pustules in an acneiform distribution as well as diffuse fine scaling of the skin. Additionally, hair growth abnormalities were noted in two patients. Histologically, a superficial purulent folliculitis and disordered differentiation with focal parakeratosis were seen. The follicular eruption appeared to respond favourably to treatment with tretinoin cream and minocycline. The cutaneous adverse effects of ZD1839 are similar to those of other EGF receptor-targeted agents and result from direct interference with the functions of EGF receptor signalling in the skin.

Acneiform Eruptions↗
PubMed2001

Mixed immunobullous disease of childhood: a good response to antimicrobials.

BACKGROUND: Immunobullous diseases are uncommon in childhood. In contrast to adults, the most commonly seen is IgA-mediated chronic bullous disease of childhood (CBDC), while IgG-mediated bullous pemphigoid (BP), cicatricial pemphigoid (CP) and epidermolysis bullosa acquisita (EBA) are rare. We have demonstrated both IgG and IgA autoantibodies to basement membrane zone target antigens in eight children with 'mixed immunobullous disease of childhood'. OBJECTIVES: To elucidate whether a dual antibody response makes these patients distinct regarding their presentation, immunopathology, course and prognosis. METHODS: We compared the eight children showing the double antibody response with 62 children with CBDC, BP, CP and EBA in whom only one antibody isotype was demonstrated. Clinical information at presentation, clinical course and response to treatment were recorded, and immunoblotting and direct and indirect immunofluorescence (IF) were performed. RESULTS: Six of the eight patients presented with clinical features of CBDC. In two others, it was uncertain whether they had CBDC or BP. Seven of the eight demonstrated a dual antibody response on indirect IF and three on direct IF. Immunoblotting revealed a variety of epidermal and dermal target antigens (BP230, BP180, 97-kDa protein and laminin 5). Five of the eight responded well to dapsone, two to sulphonamides, and one to systemic erythromycin alone. The clinical course was not protracted. Five are in remission 1-4 years following treatment, and three still have active disease suppressed by treatment after 6 months-2 years. CONCLUSIONS: Although we do not know why these children have 'mixed immunobullous disease' (the dual antibody response), our results indicate that the presence of IgA is associated with a good response to treatment with antimicrobials (dapsone, sulphonamides, erythromycin), and the clinical course is no more protracted than that found in children with a single antibody response.

Anti-Infective Agents↗
PubMed2001

Minocycline as a therapeutic option in bullous pemphigoid.

We present a retrospective analysis of patients with bullous pemphigoid (BP) treated with minocycline in the Department of Dermatology, Churchill Hospital, Oxford between July 1986 and May 2000. More than 200 patients with BP were seen in clinic during the review period. Of these, 22 patients were treated with minocycline, mostly as adjuvant therapy. The response to treatment was assessed by clinical improvement and whether the dose of concurrent immunosuppressive drugs was subsequently reduced. A major response was seen in six patients, a minor response in 11 and no response was seen in five patients. Minocycline was discontinued in four patients because of the occurrence of side-effects. Overall analysis revealed marked clinical benefits of minocycline in BP. However, this is a non-placebo controlled study and should now be followed by a prospective double-blind controlled clinical trial.

Adult↗
PubMed2000

Mixed immunobullous disease: is this linear IgA disease?

We report five patients who demonstrated clinical, histological and direct immunofluorescence (IF) features typical of linear IgA disease (LAD), but who also displayed IgG anti-basement membrane zone (BMZ) antibodies on indirect IF. The presence of circulating IgG anti-BMZ antibodies is often said to exclude the diagnosis of LAD. Unable to confidently classify these patients, we reviewed their clinical progress for unifying features. This revealed an almost universal benefit from dapsone therapy. We therefore propose that when strong linear IgA deposition is observed at the BMZ, a first line trial of dapsone is indicated, irrespective of the presence of circulating IgG. The class of antibody fixed in vivo appears to influence the clinical picture more than the class of circulating antibody.

Adolescent↗
PubMed1999

Childhood vulval pemphigoid: a clinical and immunopathological study of five patients.

We describe five girls with vulval pemphigoid: two had bullous pemphigoid confined to the vulva and three had cicatricial pemphigoid. They demonstrate a spectrum of severity from localized disease to extensive vulval scarring necessitating long-term immunosuppressive therapy and surgical correction. The age at onset of their disease ranged between 6 and 13 years. All presented with vulval discomfort and erosions. Three had oral lesions, two perianal and one eye and cutaneous involvement. Two girls with only vulval lesions and one with vulval and oral lesions responded well to topical steroids. In two, systemic treatment with prednisolone and dapsone or azathioprine was required. The diagnosis was made on the basis of histology and immunofluorescence (IF). All had positive direct IF with IgG and C3. Indirect IF demonstrated circulating IgG binding to the basement membrane zone in four, with dermal or epidermal binding on salt-split skin substrate. Immunoblotting revealed antibodies to the BP230 and BP180 antigens. Immunoelectron microscopy in the child with dermal binding IgG and BP180 and BP230 on immunoblotting showed labelling at the lamina densa-lamina lucida interface adjacent to hemidesmosomes.

Adolescent↗
PubMed1999

Three different autoimmune bullous diseases in one family: is there a common genetic base?

We report an unusual familial occurrence of autoimmune bullous diseases. Three members of a family suffered from three different autoimmune bullous diseases: pemphigus vulgaris (PV), linear IgA disease (LAD) and cicatricial pemphigoid (CP). The HLA type was determined in five family members: all were positive for HLA-DQ5/DR6, which is reported to be associated with susceptibility to PV. The CP patient was DQ7(3) positive, which is in concordance with enhanced susceptibility to ocular CP and CP. The LAD patient was B8 and DR3 negative but positive for HLA-A1. Our study supports the hypothesis that there is a genetically transmitted susceptibility to autoimmune bullous diseases but that additional factors seem necessary actually to develop a particular disease.

Adult↗