HLA-Cw6 and the genetic predisposition to psoriasis: a meta-analysis of published serologic studies.
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Genetic Predisposition to Disease↗
Biomedical subjects
E Mallon
Publications and source records attributed to E Mallon.
HLA-Cw*0602 and HIV-associated psoriasis.
The aetiopathogenesis of psoriasis is unknown, but genetic and environmental factors may be involved. Psoriasis may not be one disease but a cutaneous inflammatory reaction pattern consequent upon several different independent or related stimuli in susceptible individuals. There are controversial issues regarding the immunological basis of psoriasis and the role of CD4 vs. CD8 T lymphocytes. Psoriasis has been associated with HLA-Cw6 and Cw7 by serology and specifically with HLA-Cw*0602 by polymerase chain reaction (PCR) typing. Psoriasis is probably no more common in HIV infection than in the general population; however, it may appear for the first time or pre-existing psoriasis may worsen and be difficult to treat in HIV disease. We have investigated the prevalence of HLA-C alleles, in the specific clinical context of HIV infection complicated by type 1 psoriasis, in a case control study of 14 men with HIV disease and type 1 psoriasis and 147 HIV-infected patients without psoriasis. Typing was performed using PCR with sequence-specific amplification primers. Eleven of 14 patients (79%) with psoriasis carried the HLA-Cw*0602 allele compared with 24.5% of those without psoriasis (odds ratio = 11.31; 95% confidence limits 2. 73 to 65.36; P = 0.0001). Two patients without the HLA-Cw*0602 allele carried instead the closely related Cw*0401/3 allele. The results confirm the previously reported association between the HLA-Cw*0602 allele and type 1 psoriasis, and suggest that the association with HLA-Cw*0602 is stronger in HIV-associated psoriasis although this trend needs to be supported by a larger sample. The immunodysregulation resulting from HIV infection may trigger psoriasis in those genetically predisposed by the Cw*0602 allele. As CD8 T cells recognize antigens in the context of class I major histocompatibility complex, the identification of an HLA class I association in HIV-associated psoriasis strengthens the argument for an important role for CD8 + T lymphocytes in the immunopathogenesis of psoriasis. Investigations of the pathogenesis of psoriasis should take account of clinical and other subtypes already identified.
Adult↗
Combination therapy with nicotinamide and tetracyclines for cicatricial pemphigoid: further support for its efficacy.
We have previously reported the reduction of cicatricial pemphigoid orodynia with minocycline. Tetracycline combined with high dose nicotinamide has also been beneficial in a number of cutaneous immunological disorders. We now report a series of eight cases in whom further subjective or clinical improvement accrued in five, after the addition of high dose (2.5 or 3 g) nicotinamide to minocycline; however, one of these then discontinued the nicotinamide because of headache and nausea, another was withdrawn from the study because of progressive upper respiratory tract mucosal involvement, and two were changed from minocycline to tetracycline because they developed minocycline-induced hyperpigmentation.
Aged↗
Extraordinary case report: cutaneous anthrax.
Anthrax is a very rare disease in the United Kingdom. It is caused by the spore-forming bacterium Bacillus anthracis. Humans become infected when they come into contact with infected animals or their products. Cutaneous anthrax, the most common form of the disease, accounts for 95% of cases, and the disease usually developing on exposed sites. We present a patient who developed cutaneous disease after exposure to untreated leather. Owing to the initial clinical information, the biopsy specimen was misinterpreted as representing a severe acute insect bite reaction. The subsequent involvement by the Department of Microbiology established the correct diagnosis. Because today the disease is so rare in Europe and the United States, sporadic cases of anthrax are easily overlooked as the diagnosis often is not considered. Cutaneous anthrax should be considered in any patient with a painless ulcer with vesicles, edema, and a history of exposure to animals or animal products.
Anthrax↗
HLA-CW*0602 is a susceptibility factor in type I psoriasis, and evidence Ala-73 is increased in male type I psoriatics.
We investigated the HLA-C locus of 87 unrelated patients with chronic plaque psoriasis by genotyping with sequence-specific amplification primers. The HLA-Cw*0602 allele was significantly increased in male and female type I psoriatics but not significantly increased in either male or female type II psoriatics. The overall frequency of Ala-73 (present in Cw*04, Cw*0602, Cw*07, Cw*12, Cw*1503, and Cw*17) in psoriatics was 88.5% but the incidence of Ala-73 in our Caucasian controls was also high at 84.3%. Ala-73 was present in 97.2% of type I and 85.7% of type II male psoriatics (chi2 = 8.43, p = 0.001; chi2 = 0.01, p = nonsignificant, respectively), in contrast to 81.5% of type I and 80% of type II female psoriatics (nonsignificant). HLA-Cw*0602 appeared more discriminating in determining disease susceptibility in our population than Ala-73, in line with earlier serologic studies implicating HLA-Cw6. Thus, although the frequency of HLA-Cw*0602 decreased from 54.0% in type I to 29.2% in type II psoriatics, the overall frequency of Ala-73, present in 90.4% of type I and 83.3% of type II psoriatics, did not. (i) Thus this study confirms the strong association between psoriasis and HLA-Cw*0602 by using sequence-specific amplification primers. (ii) Results show that Ala-73 on HLA-C molecules is increased in frequency in psoriasis, but results observed show an association more subtle than previously thought, with HLA-Cw*0602 playing the major role. (iii) This report documents the differential association of HLA genes in male and female psoriatic patients. An interaction between gender and immunogenetics may influence susceptibility to psoriasis.
Alleles↗
The effectiveness of acne treatment: an assessment by patients of the outcome of therapy.
The impact of acne on quality of life can be profound. Although treatment improves the clinical features of acne, there is little information on its benefit from the patients' point of view. In this study, patients with acne referred to a dermatology clinic were sent questionnaires before being seen, and 4 and 12 months afterwards. Clinical severity was assessed by a dermatologist at baseline and at 4 months. Quality of life was assessed by patients using the Short Form 36 instrument (SF-36), the Dermatology Life Quality Index (DLQI), Rosenberg's measure of self-esteem and the General Health Questionnaire (GHQ-28). Of 90 available patients, 79 (89%) returned at least one follow-up questionnaire. The clinical acne grade improved substantially with treatment. There were also significant improvements either at 4 or 12 months in the DLQI, self-esteem. GHQ-28 and all five dimensions of the SF-36 that were impaired at baseline. Quality of life continued to improve between the 4- and 12-month follow-up questionnaires. Clinical and patient-assessed outcomes were significantly better in patients treated with isotretinoin. The study showed that disability caused by acne can be largely reversed by effective treatment. It also showed that patient-assessed measures of outcome can respond to changes over time and discriminate between treatments differing in effectiveness.
Acne Vulgaris↗
Development of PCR-SSOP for HLA-A typing of bone marrow registry donors.
A medium resolution PCR-SSOP typing method, using 26 digoxigenin labelled probes, has been established for the identification of HLA-A alleles. The system is capable of discriminating all of the serologically defined specificities except for eight heterozygous combinations which are however rare in Caucasians. The method has been applied to 1,838 individuals on the local bone marrow registry who either had only one detectable HLA-A antigen, or a HLA-A antigen whose presence had been queried using the serological technique or a broad HLA-A specificity assigned by the serological technique. In all but one case the serologically assigned antigens were detected with the PCR-SSOP method. In addition, PCR-SSOP detected the presence of a second HLA-A allele in over 10% of individuals who had been previously homozygous. Frequency information, based on a population of 5,000 individuals, has been established using a combination of molecular and serological typing data.
Bone Marrow↗
Biopsy of male genital dermatosis.
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Adolescent↗
Tumour bed positivity predicts outcome after breast-conserving surgery.
BACKGROUND: Local recurrence after breast-conserving surgery is associated with a short distant disease-free survival, particularly if it occurs early. Early recurrence is caused by residual disease left at the time of surgery. Previous studies have demonstrated that disease in the tumour bed is a common finding after breast-conserving surgery. METHODS: The follow-up (mean 4.4 years) of 300 patients who had tumour bed analysis performed by the cavity shaving technique following breast-conserving surgery is presented. Postoperative radiotherapy was administered to all patients. RESULTS: The incidence of tumour bed positivity was 39.3 per cent. With a selective re-excision policy the local recurrence rate was 2.0 per cent and distant recurrence rate 10.4 per cent. Multivariate analysis identified lymphovascular invasion, oestrogen receptor status and tumour bed status as independent predictors of time to distant recurrence. CONCLUSION: A low rate of local recurrence can be achieved using this technique of margin assessment. Tumour bed status may be a useful prognostic factor following breast-conserving surgery.
Adult↗
Evidence for altered cell-mediated immunity in postmastectomy lymphoedema.
Patients with chronic lymphoedema are prone to develop chronic infections and various tumours in the lymphoedematous limb, suggesting that regional immune surveillance is impaired. To test the hypothesis that cutaneous cell-mediated immunity is impaired, 35 women with postmastectomy lymphoedema were investigated using dinitrochlorobenzene to test the afferent and efferent loops of the allergic contact immune response. The results support the role of lymphatics as an important component of the immune response to allergens by the demonstration of impairment of both the afferent and efferent loops of the allergic contact dermatitis reaction, and confirm that there is suppression of immune competence in a lymphoedematous limb.
Adult↗
Hepatocyte growth factor/scatter factor expression and c-met in primary breast cancer.
Hepatocyte growth factor/scatter factor (HGF/SF) is a fibroblast-derived cytokine whose receptor is encoded by c-met. Activation of c-met promotes tumour cell proliferation, dissociation, invasiveness and angiogenesis. Aberrant expression of HGF/SF or c-met may play a role in tumour progression. HGF/SF and c-met were determined in 73 breast cancers (median follow up: 61 months) and 10 samples of tumour-free breast tissue. HGF/SF was detected at significantly higher concentrations in breast cancers (median 350, range 58-1604 ng per 100 mg total protein) when compared with normal breast tissue (median 108, range 66-213 ng per 100 mg total protein) (P < 0.001). C-met was detected in all 10 samples of tumour-free breast tissue and in 26 breast cancers. HGF/SF concentrations correlated with disease relapse (P < 0.001) and reduced overall survival (P < 0.001). Tumours with detectable c-met correlated significantly with disease-relapse (P = 0.012). Multivariate analysis demonstrated a significant interaction between HGF/SF and c-met in relation to disease-relapse (P = 0.014). These results suggest a biological interaction involving HGF/SF and c-met in promoting tumour progression in breast cancer.
Breast↗
Vulval cicatricial pemphigoid may mimic lichen sclerosus.
We report two patients with vulval signs suggestive of lichen sclerosus. This diagnosis was never substantiated histologically and microscopic appearances were non-specific. In both cases the development of lesions at other cutaneous and mucosal sites alerted us to the possibility that the autoimmune bullous disease, cicatricial pemphigoid, accounted for the entire clinical picture. Lichen sclerosus and cicatricial pemphigoid are distinctive conditions which clinically are usually readily differentiated on cutaneous surfaces. When the site of presentation is on the vulva the clinical picture may become obscure and this can lead to diagnostic confusion. It is important to establish the correct diagnosis as this predicts the clinical course and prognosis in each case.
Aged↗
Cystosarcoma phylloides: heterogeneity in a rare tumour type.
Mammary cystosarcoma phylloides is a rare tumour, and clear guidelines for its clinical management are lacking. We present three cases from the Western Infirmary which illustrate the range of behaviour that these tumours can manifest, and discuss some of the clinical problems that they present.
Adult↗
Cryosurgery in the treatment of basal cell carcinoma. Assessment of one and two freeze-thaw cycle schedules.
BACKGROUND: It has become routine practice in many centers to use two successive freeze-thaw cycles in the treatment of the common types of basal cell carcinoma. Because of the potential morbidity caused by this, we have investigated the cure rate achieved with one freeze-thaw cycle compared with that achieved with two freeze-thaw cycles in the treatment of facial basal cell carcinomas of a uniform type and clinically in the best prognostic group. Superficial truncal basal cell carcinomas are reported to respond to less aggressive cryosurgery, and we have investigated the cure rate achieved with one freeze-thaw cycle. OBJECTIVE: To compare the efficacy of one freeze-thaw cycle versus two freeze-thaw cycles in the treatment of facial basal cell carcinomas. Second, to investigate the efficacy of one freeze-thaw cycle in the treatment of superficial truncal basal cell carcinomas. This was investigated in a prospective randomized post-treatment follow-up study. METHODS: Over the past 7 years, we have treated 84 facial basal cell carcinomas with either a single 30-second freeze-thaw cycle or a double 30-second freeze-thaw cycle. Patients were allocated randomly into one of the two treatment schedules, and the cure rates achieved were compared. Second, 29 superficial truncal basal cell carcinomas were treated with a single 30-second freeze-thaw cycle. Patients were followed up to assess response to therapy. RESULTS: A 95.3% cure rate was achieved in the treatment of facial basal cell carcinomas with a double freeze-thaw cycle. This compared with a cure rate of only 79.4% when facial lesions were treated with a single freeze-thaw cycle. Treatment of superficial truncal basal cell carcinomas with a single freeze-thaw cycle achieved a cure rate of 95.5%. CONCLUSION: We recommend that, in order to achieve high cure rates that are equivalent to many reports of formal excision or radiotherapy, facial basal cell carcinomas require a double freeze-thaw cycle with liquid nitrogen. One freeze-thaw cycle to truncal basal cell carcinomas achieves high cure rates, equal to that achieved with a double freeze-thaw cycle to facial basal cell carcinomas.
Aged↗
Neonatal bullous eruption as a result of transient porphyrinemia in a premature infant with hemolytic disease of the newborn.
We describe the clinical and biochemical features of an infant with marked transient porphyrinemia in whom blistering developed while the infant was undergoing phototherapy for severe Rh isoimmunization. The cause of the transient porphyrinemia was likely to be multifactorial--abnormal porphyrin metabolism or accumulation in a premature infant with multisystem disease and multiple drug therapy. In addition, the infant received an unusually large amount of phototherapy. No evidence for an associated porphyria has been obtained. We believe this is a unique case because transient porphyrinemia associated with neonatal blistering does not appear to have been reported previously. Furthermore, blistering associated with phototherapy is rare.
Erythroblastosis, Fetal↗
Modification of an HLA-B PCR-SSOP typing system leading to improved allele determination.
Modifications have been introduced to a previously reported HLA-B PCR-SSOP typing system. This has enabled further definition of alleles, determination of the probe pattern of some alleles not previously examined and identification of patterns of possible new alleles. However there are still some alleles that cannot be differentiated and there are several alleles which when present as a homozygote have the same pattern as in combination with another allele. When the method was applied to the typing of 66 consecutive cadaveric donors there were three donors whose type differed from the serological type.
Alleles↗
Predicting local recurrence by correlating pre-operative mammographic findings with pathological risk factors in patients with breast cancer.
The pre-operative mammograms for 231 patients undergoing conservation surgery for breast cancer between March 1988 and September 1992 were analysed for features that may predict the presence of pathological risk factors of local recurrence (residual microscopic disease, extensive intraduct carcinoma (EIC) and lymphatic/vascular invasion). Residual microscopic disease was detected in 40% of patients and was associated with a DY mammographic pattern (p = 0.03), casting calcification (p = 0.0002) and absence of mammographic nidus (p = 0.0006). Residual microscopic disease was found in 75-88.9% of patients when two of these preoperative mammographic features were present in combination. The mean lumpectomy diameter was significantly smaller for patients with DY compared to N1 mammographic pattern on Wolfe grade (p = 0.039). Both residual disease and Wolfe grade were related to age (p = 0.0032 and p < 0.0001). EIC was found in 22% of patients and was associated with casting (p < 0.0001) and non-casting (p = 0.04) calcification, absence of mammographic nidus (p < 0.0001) and stellate mammographic nidus (p = 0.02). No significant association was found between mammographic features and lymphatic/vascular invasion. Pre-operative mammographic features can predict patients likely to have residual microscopic disease or EIC following conservation surgery for breast cancer. These patients should be selected for wider primary excision.
Adult↗
Breast-conserving surgery and tumour bed positivity in patients with breast cancer.
Between March 1988 and April 1992, in 264 patients undergoing breast-conserving surgery for stage I and II cancer, the tumour bed was analysed for residual disease. After a conventional breast-conserving operation the entire wall of the cavity from which the lumpectomy specimen had been taken was excised. This was involved with disease in 38 per cent of patients. Additional random biopsies of the secondary cavity were performed in 130 patients and were involved with disease in 13 per cent. Residual disease was detected in the tumour bed of 37 per cent of patients with screen-detected tumours.
Adult↗