Biomedical subjects
Publications and source records attributed to A D Ormerod.
A case of cutaneous cryptococcosis (encapsulated strain) in a 67-year-old female, with no evidence of immune suppression (normal cell surface marker analysis and mitogen proliferation studies) and which responded to treatment with oral fluconazole is reported. To date her clinical progress remains satisfactory after 12 months of follow-up.
In the past 4 years, a high incidence (118/362) of positive patch test reactions to E45 cream were noted in 2 patch testing clinics. 18/54 of those patch tested to all the ingredients demonstrated allergies to ingredients. The most frequent was triethanolamine; lanolin allergy occurring in only 1 patient. The remaining reactions may be explained as irritant reactions resulting from triethanolamine stearate (TES) formation within the cream. The irritancy of triethanolamine stearate was demonstrated in patients and controls. Conductivity studies showed that TES arises from the combination of the ingredients triethanolamine and stearic acid. The formulation of E45 cream was being changed at the time of writing, with the removal of triethanolamine from the product.
The urticarias are a complex group of disorders characterised by transient whealing or swelling of the skin. Understanding the many possible causes is the first step in assessing urticaria. Allergic and drug-induced urticaria respond to removal of the cause. The physical urticarias, particularly delayed pressure urticaria and also urticarial vasculitis, require separate consideration. For the majority of patients with chronic idiopathic urticaria, nonsedating antihistamines are the mainstay of treatment. There are several to choose from, including cetirizine, astemizole, loratadine, terfenadine and acrivastine, each with its own pharmacokinetics and antiallergic properties. When these fail, histamine H2-antagonists may help either alone or in combination with H1-antagonists. Older sedative antihistamines are still useful. Ketotifen, oxatomide and azelastine have mast cell stabilising effects that are considered an advantage in treating these disorders. Second-line therapies include a wide range of drugs such as doxepin, dapsone, attenuated androgens, calcium antagonists, antimalarials, gold and methotrexate. The most effective and regularly used second-line agents are corticosteroids. These are best limited to short term crisis management, except in severe recalcitrant cases, and in patients with pressure urticaria or urticarial vasculitis. Recent work on circulating histamine releasing autoantibodies suggests that there is scope for more aggressive immunosuppression in selected patients. However, effective treatment with immunosuppression often requires plasma exchange and more toxic agents such as cyclosporin. Such treatments are only likely to be entertained in exceptional cases.
BACKGROUND: Familial cold urticaria is a rare cutaneous and systemic reaction to cold with autosomal dominant inheritance, distinctive clinical features, and unknown pathogenesis. Release of a chymotrypsinlike substance has been postulated. To date, no effective treatment has been reported. OBSERVATIONS: Eight cases from a large family pedigree are described. Three members showed a very favorable response in their cold urticaria, when treated with stanozolol; the response was reproducible. Histologic examination of an early lesion in one case revealed evidence of mast cell degranulation. CONCLUSIONS: The biochemical observations are probably secondary epiphenomena. Correction of a deficiency of an inhibitory protein is a possible mechanism of action of stanozolol as in hereditary angioedema.
Following the observation of increased trough whole blood cyclosporin A (CyA) concentrations and reduced renal function in a patient with recalcitrant generalized pustular psoriasis treated with a combination of CyA and etretinate, the effect of vitamin A analogues on human microsomal cytochrome P450-dependent CyA metabolism was investigated in vitro. In addition, the effect of terbinafine, a new allylamine antifungal agent, was also tested. Etretinate, its major metabolite acitretin, and isotretinoin, each at a single concentration of 100 microM, inhibited total hepatic microsomal CyA metabolism to a similar extent (33-45%, compared with control values). The generation of total primary and total secondary CyA metabolites was also inhibited to a similar extent by each of the retinoids. Conversely, terbinafine was without significant effect on CyA metabolism in vitro. The results, which suggest that inhibition of hepatic CyA metabolism by retinoids may contribute to increased circulating CyA concentrations, are discussed in relation to other potential drug interactions, and to the use of etretinate in reducing the CyA administered dose.
Topical cyclosporin A (CyA; Sandimmun) in a formulation incorporating the penetration enhancers (PE) propylene glycol (18%) and azone (2%) was tested for efficacy in a double-blind, vehicle-controlled trial in 5 chronic plaque psoriatic patients. On each patient, two similar plaques were treated daily, under occlusion, for 4 weeks with either 8% (w/v) CyA, containing PE, or with vehicle comprising olive oil with PE. All sites improved significantly, but there was no significant difference between those receiving active and control preparations. Cryostat sections of biopsies performed after 4 weeks' treatment showed significant reductions in CyA compared with vehicle-treated sites in the number of cells, positive for CD3 and CD25 in the epidermis and CD25 and HLA-DR in the dermis. These results suggest that amounts of CyA adequate to affect the lymphocytic infiltrate penetrated the epidermis but that only partial suppression occurred in the dermis, as indicated by the reduction in lymphocyte activation status.
Relapsing polychondritis is a rare disease which often presents firstly to ear, nose and throat (ENT) departments. Its complications, respiratory, cardiovascular, renal and neurological are life-threatening; thus it is important to recognize the disease and its complications early. Treatment for relapsing polychondritis may have serious side-effects which should be taken into account when managing these patients. We report two young patients with relapsing polychondritis and their treatments; both had severe tracheal stenosis responding in one case to pharmacological and in the other to surgical intervention.
Explore the source record for details and available documents.
Erythema gyratum repens (EGR) is a cutaneous manifestation of malignant disease. We report an unusual accumulation of activated epidermal Langerhans cells in the upper layer of the epidermis and propose that these cells play an important immunopathological role.
Toxic epidermal necrolysis (TEN) is a severe life-threatening disorder which has many features in common with graft-versus-host disease. However, immunosuppression with steroids gives disappointing results and is possibly detrimental. We treated two patients who had TEN with a combination of cyclosporin and steroids which resulted in an apparent halt to the evolution of the disease, and a further relapse was aborted using cyclosporin in one of these patients. We feel that the use of this drug in the early treatment of TEN where it is used as a specific therapy aimed at the primary immunopathological events and is used in conjunction with the supportive care patients require, needs to be further evaluated.
Explore the source record for details and available documents.
We report the association of erythema elevatum diutinum (EED) with ulcerative colitis (UC). The patient, whose history included rheumatoid disease, diabetes mellitus (type I) and hypothyroidism developed EED during a severe acute exacerbation of UC which resolved following colectomy. To our knowledge this is the first report of such an association. Also of interest was the observation of Köebner phenomenon occurring at the sites where blood vessels were damaged.
A study was conducted to quantify soluble IL-2 receptor (sIL-2R) levels in sera of 57 chronic plaque psoriasis patients and correlate these measurements with disease activity and the number of IL-2R-positive (CD25+) lymphocytes in lesional biopsies of 11 cyclosporin A (CsA) and 13 psoralen plus ultraviolet radiation (PUVA) treated patients. Levels of sIL-2R showed a strong correlation with the psoriasis area and severity index (PASI). CsA and PUVA significantly reduced the PASI and sIL-2R levels to a similar degree after 4 weeks of treatment. Although the majority of CsA-treated patients who were biopsied showed reductions in lesional CD25+ cells, these did not reach statistical significance; in five patients biopsied who had PUVA treatment, no consistent effect on the numbers of CD25+ cells was observed. A significant correlation was found between CD25+ cells in lesional biopsies and the PASI score.
Systemic administration of cyclosporine A (Cy-A; initial dose 5 or 2.5 mg/kg/day) to patients with severe chronic plaque psoriasis produced marked reductions in psoriasis area and severity index within 4 weeks. The clinical response was accompanied, within 1 week, by progressive reductions in T-cell subpopulations (CD3+ and CD4+) and in numbers of interleukin-2 receptor (IL-2-R)-positive (CD25+) cells within lesional skin. Over the first 4 weeks of treatment, these changes were accompanied by reductions in DR+ cells within the epidermis (minor) and dermis (substantial). In contrast, numbers of epidermal CD1+ cells increased substantially during resolution of the skin lesions. Unlike lesional skin, however, no significant changes in absolute numbers of circulating immunoregulatory T-cell populations, including helper/inducer (CD45R) and suppressor/inducer (CD29W) subsets, quantified by dual immunofluorescence labelling, were detected. Moreover, numbers of blood-borne HLA-DR, IL-2-R and transferrin receptor (CD71) positive lymphocytes were unaffected by Cy-A therapy, nor were any differences detected between psoriatic patients and normal controls using these cell markers. Our data suggest that the immunoregulatory effects of Cy-A in psoriasis are mediated via lesional T lymphocytes and that epidermal CD1+ DR- dendritic cells may play an influential role in the regulation of T-cell function and keratinocyte growth during resolution of the skin lesions.
No clinically successful topical cyclosporin A (CyA) formulation has been produced, mainly due to the apparent lack of drug penetration. This study has produced the first in vitro kinetic data on CyA penetration across human cadaver stratum corneum and has shown that addition of the penetration enhancers (PE) Azone and propylene glycol to the CyA vehicle significantly enhanced drug permeation across the skin barrier. Using flow-through permeability cells with 5% w/v CyA (Sandimmun) alone (CyA) or with PE (CyA + PE) in olive oil in the donor chamber, the penetration rate (mean +/- SD microgram/cm2/h) into receptor fluid was 53 +/- 43 (n = 13) for CyA and 660 +/- 175 (n = 7) for CyA + PE. The in vivo efficacy of this formulation was assessed in guinea-pigs undergoing delayed-type hypersensitivity (DTH) reactions to dinitrofluorobenzene (DNFB). CyA was applied topically at the time of challenge and twice daily thereafter. At 24 h, skin reactions revealed that compared with appropriate drug vehicles, concentrations of 0.25, 0.5 and 5% CyA +/- PE had a significant inhibitory effect upon the erythema response and this corresponded with significant reductions in T-cell infiltrates (0.5 and 5% CyA). No statistically significant reductions in erythema were demonstrated with 0.05% CyA +/- PE, but there was a reduction in the number of infiltrating lymphocytes in sites receiving 0.05% CyA + PE compared with vehicle-treated sites (P less than 0.01). This suggests that PE permitted some penetration of an otherwise non-immunosuppressive concentration of CyA through the skin.
Skin mast cells of five patients with mastocytosis/urticaria pigmentosa and from four normal controls were immunophenotyped with a panel of 17 monoclonal antibodies; peripheral blood mononuclear cells from the patients were similarly labelled and analysed by flow cytometry. Cutaneous mast cells expressed leucocyte common antigen and markers of macrophage/monocyte lineage suggesting a common progenitor in the ontogeny of the two cell types. The mast cells from the patients differed from the controls, expressing HLA-DR in four cases, and this may be a feature of proliferating cells. The patients' peripheral blood T lymphocytes showed a marked increase in the activation markers HLA-DR and CD25 suggesting a contributory role, possibly via cytokines, in driving mast-cell proliferation.
Explore the source record for details and available documents.
Oil-based mud, a complex mixture containing amines in emulsifiers, is used in offshore drilling operations. It is a skin irritant that occasionally gives rise to allergic contact sensitivity. In patch testing patients with allergy to drilling mud, we have identified polyamine (diethylenetriamine and triethylenetetramine) sensitivity in 5 patients. All 5 patients were also allergic to emulsifiers. These emulsifiers are cross-linked fatty acid amido-amines, in which unreacted amine groups are thought to cross-sensitize with these constituent polyamines. Cross-reactivity between ethylenediamine, diethylenetetramine and triethylenetetramine was found in 9 subjects.