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PubMed2002

Tetrazepam drug sensitivity -- usefulness of the patch test.

The muscle relaxant tetrazepam may cause severe cutaneous adverse effects. We report 4 cases of varying intensity: Stevens-Johnson syndrome, erythema-multiforme-like exanthema, maculopapular and maculo-urticarial exanthema. Patch testing with tetrazepam (10% in petrolatum) was strongly positive in the 2 patients with severe skin eruptions and weakly positive in the other 2. Oral rechallenge with tetrazepam was positive in 3 patients (1 not done). Diazepam, with a similar chemical structure to tetrazepam, was negative on patch testing and on oral challenge testing in 2 patients. Although the optimal patch test concentration of tetrazepam has still to be determined, it is a useful diagnostic tool to confirm sensitization, particularly in patients with severe bullous eruptions.

Administration, Oral↗
PubMed2003

Clinical and immunologic features of systemic contact dermatitis from ingestion of Rhus (Toxicodendron).

Oral or parenteral exposure to certain contact allergens may elicit an eczematous skin reaction in sensitized individuals. This phenomenon has been called systemic contact dermatitis (SCD) and is relatively rare when compared with classical contact dermatitis. We reviewed and analysed the clinical and immunologic features of 42 patients with SCD caused by ingestion of Rhus (Toxicodendron), 24 males and 18 females, average age 44 years (range 24-72). Several of such patients (33%) had a known history of allergy to lacquer. The patients developed skin lesions such as generalized maculopapular eruptions (50%), erythroderma (29%), vesiculobullous lesions (14%) and erythema multiform (EM)-like lesions (7%). Many patients (57%) developed leucocytosis with neutrophilia (74%). In some patients (5%), abnormalities of liver function developed. We also analysed lymphocyte subsets in the peripheral blood of 12 patients. The lymphocyte subsets studied were T cells (CD3), B cells (CD19), natural killer (NK) cells (CD3-CD16+/CD56+), helper/inducer cells (CD4), cytotoxic/suppressor cells (CD8) and helper/suppressor ratio (CD4/CD8). The lymphocyte subsets of all 12 patients studied were within the normal range. Moreover, there were no differences between patients with a history of allergy to lacquer and those without a history of allergy to lacquer. Therefore, rather than an immunologic response, the skin eruption seems to be caused by a toxic reaction because of Rhus.

Administration, Oral↗
PubMed2003

Internalization via plasmalemmal vesicles: a route for antidesmoplakin autoantibodies into cultured human keratinocytes.

Recently, autoantibodies to desmoplakin I and II have been identified in a subset of patients with a severe form of erythema multiforme. These autoantibodies recognize a specific peptide sequence at the carboxy terminal domain of desmoplakin I and II responsible for interaction with keratin filaments. Desmoplakins are major constitutive proteins of the inner dense desmosomal plaque of keratinocytes and are entirely localized within the cells. With the assumption of pathogenecity for circulating autoantibodies, the question arose how antidesmoplakin autoantibodies enter keratinocytes. Utilizing immunhistochemical procedures for cell motility and time kinetic studies at the light- and electron-microscopic level, we found that autoantibodies are bound at the cell surface of cultured human keratinocytes, internalized via plasmalemmal vesicles, and are found consecutively within tubulovesicular structures inside the cells. At the same time, a fraction of antibodies can be detected at the inner dense desmosomal plaques. Immunogold labeling reveals internalization of autoantibodies in small non-coated plasmalemmal vesicles positive for caveolin. These observations indicate that vesicular transport may represent a relevant biological mechanism for antidesmoplakin autoantibodies to enter keratinocytes and allow access to their corresponding antigenic target in vivo.

Autoantibodies↗
PubMed2003

Infusion of plasma-derived mannan-binding lectin (MBL) into MBL-deficient humans.

Our first experience of mannan-binding lectin (MBL)-replacement therapy was with a patient experiencing recurrent erythema multiforme associated with reactivation of herpes simplex virus; his erythematous eruptions could be controlled with infusions of fresh frozen plasma containing MBL, but not with plasma lacking MBL. Some years later, we treated a young girl with recurrent, debilitating infections with purified MBL; this was also followed by a dramatic clinical improvement. We have now carried out a phase I clinical trial on 20 MBL-deficient, but healthy, adult volunteers. The MBL was prepared by the State Serum Institute in Copenhagen, Denmark, from blood donor plasma. Each volunteer received a total of 18 mg of MBL in three 6-mg doses given intravenously once a week over 3 weeks. The volunteers were monitored closely after each infusion and no adverse clinical or laboratory effects were observed. Laboratory parameters included C-reactive protein, various complement components, and antibodies to MBL, HIV and hepatitis viruses. C3a (the anaphylotoxin derived from complement component C3) was monitored for signs of complement activation, but no significant infusion-associated fluctuations were observed. Serum levels of MBL after each 6-mg infusion ranged between 1200 and 2500 ng/ml. The half-life of the infused MBL was about 70 h, or 3 days. It was concluded that infusion of purified MBL manufactured by the Danish State Serum Institute is a safe procedure. However, adults may have to be given 6 mg or more at least twice weekly to maintain protective plasma MBL levels in MBL-deficient individuals.

Clinical Trials, Phase I as Topic↗
PubMed2002

Retrospective study: the presence of Malassezia in feline skin biopsies. A clinicopathological study.

Malassezia spp. dermatitis, a rare disorder in cats, has previously been associated with immune suppression and internal malignancies. This study evaluates the presence and importance of Malassezia spp. in feline biopsy specimens submitted for histopathological examination. Five hundred and fifty haematoxylin and eosin-stained skin biopsy specimens received for histopathological examination between January 1999 and November 2000 were reviewed. Fifteen (2.7%) submissions contained Malassezia organisms in the stratum corneum of the epidermis or follicular infundibulum. Eleven of 15 cats presented with an acute onset of multifocal to generalized skin lesions. All 11 cats were euthanized or died within 2 months of the onset of clinical signs. Seven cats had dermatopathological changes and clinical signs supportive of paraneoplastic alopecia, and three cats had an interface dermatitis suggestive of erythema multiforme or thymoma-associated dermatosis. Histopathological changes were nonspecific in one cat that was euthanized 2 weeks following onset of severe pruritus and alopecia. In three cats, Malassezia spp. were found in localized sites (two chin, one footpads) and appeared inconsequential to their overall health status. One cat had Malassezia spp. in association with cutaneous demodicosis. These findings suggest that Malassezia yeast in dermatopathological specimens from multifocal or generalized lesions should prompt a thorough clinical work-up for internal neoplasia.

Animals↗
PubMed1999

Cutaneous reactions to drugs. An analysis of spontaneous reports in four Italian regions.

AIMS: Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day. RESULTS: A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics. CONCLUSIONS: Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.

Anti-Bacterial Agents↗
PubMed1998

Chronic staphylococcal scalded skin syndrome.

Staphylococcal scalded skin syndrome (SSSS), not previously recorded as a chronic disease, persisted for 2 years in a 50-year-old woman with epilepsy and cerebellar ataxia. Lesions initially suggestive of erythema multiforme and toxic epidermal necrolysis evolved over 2 years into those typical for SSSS, with extensive erosions and subcorneal blisters, showing an epidermal split at the granular cell layer. Exfoliatin A-producing phage I-III Staphylococcus aureus, previously linked only to acute mild adult cases of SSSS, was cultured from purulent discharge in the patient's eyes, ears and open skin lesions. The roles of epilepsy and antiepileptic medications are discussed as possible predisposing factors.

Anticonvulsants↗
PubMed2000

Clinical features of 31 patients with systemic contact dermatitis due to the ingestion of Rhus (lacquer).

In Korea, Rhus has been used as a folk medicine to cure gastrointestinal diseases and as a health food. We review the clinicopathological and laboratory findings in patients with systemic contact dermatitis caused by intake of Rhus. We reviewed medical records and histopathological sections from 31 patients during a 10-year period. The male/female ratio was 1.4: 1 and the average age was 43.8 years (range 22-70). Ten patients (32%) had a known history of allergy to lacquer. Rhus was ingested to treat gastrointestinal problems including indigestion and gastritis (45%), and as a health food (39%), in cooked meat, in herbal medicine, or taken by inhalation. The patients developed skin lesions such as a maculopapular eruption (65%), erythema multiforme (EM, 32%), erythroderma (19%), pustules, purpura, weals and blisters. Erythroderma was very frequent in patients with a known history of allergy to lacquer, but maculopapular and EM-type eruptions were more frequently observed in those without a history of allergy. All patients experienced generalized or localized pruritus. Other symptoms included gastrointestinal problems (32%), fever (26%), chills and headache; many developed leucocytosis (70%) with neutrophilia (88%), while some showed toxic effects on liver and kidney. Fifty-nine per cent of patients observed cutaneous or general symptoms within a day after ingestion of Rhus. There was no difference in the time lag for symptoms to develop between patients allergic and not allergic to Rhus. All patients responded well to treatment with systemic steroids and antihistamines. Common histopathological findings were vascular dilatation, perivascular lymphohistiocytic infiltration, and extravasation of red blood cells in the upper dermis. Rhus lacquer should not be ingested in view of its highly allergic and toxic effects.

Administration, Oral↗
PubMed2000

Rupert Hallam and the development of dermatology in Sheffield.

(Arthur) Rupert Hallam worked as a dermatologist in Sheffield from 1911 to 1944. Early in his career, he also specialized in diagnostic radiology and established this speciality in Sheffield. Hallam performed investigative work on the aetiology of papular urticaria and erythema multiforme, the prognosis of psoriasis, and the aetiology of chilblains. He was an original member of the British Association of Dermatologists from 1920 becoming president in 1935. He also helped to found the North of England Dermatological Society. He was an innovator in both clinical and administrative matters and was the first British dermatologist to develop a full-time training post in the specialty.

Dermatology↗
PubMed2000

Treatment of psoriasis with oral liarozole: a dose-ranging study.

BACKGROUND: Liarozole is an inhibitor of the metabolism of all-trans-retinoic acid. Systemic administration increases tissue levels of this endogenous retinoid and has been reported to improve psoriasis in an open, uncontrolled study. OBJECTIVES: A multicentre, double-blind, placebo-controlled, dose-ranging study was therefore undertaken to determine the lowest effective oral dose of liarozole in the treatment of psoriasis vulgaris. PATIENTS/METHODS: Adult male and postmenopausal female patients requiring systemic treatment for psoriasis were randomized to receive placebo or liarozole at total daily doses of 50 mg, 75 mg or 150 mg for 12 weeks. The daily doses were each divided into two equal (morning and evening) doses. Response was assessed using an eight-point global scale to assess improvement and by monitoring the Psoriasis Area and Severity Index (PASI). The primary end-point was the proportion of subjects in each treatment group demonstrating 'marked improvement' or better as assessed on the eight-point scale. The tolerability of the treatment was assessed by recording mucocutaneous effects of retinoids and all adverse events. Biochemical and haematological monitoring were also performed. RESULTS: One hundred and thirty-nine subjects were randomized (118 male and 21 female) and 116 completed the study. A marked improvement or better response was observed in 6% of subjects on placebo, 18% on liarozole 50 mg, 11% on 75 mg and 38% on 150 mg. Only in the 150-mg group was the response rate significantly different to placebo (P < 0.001). Over the treatment period the mean PASI changed from 15.9 to 15.4 on placebo, from 17.4 to 13.8 on liarozole 50 mg, from 17.5 to 14.5 on 75 mg and from 15.8 to 8.8 on 150 mg. Again, only in the group receiving 150 mg was the response significantly better than placebo (P < 0.001). Liarozole was generally well tolerated. Mucocutaneous retinoid effects were generally infrequent and mild. Five subjects were withdrawn from treatment as a result of adverse events that may have been treatment related. These events were abnormalities of liver enzymes in two cases, an episode of erythema multiforme (in a patient receiving placebo), an allergic reaction in one and a rash accompanied by deterioration of the psoriasis in another. There was mild elevation of triglycerides in the groups receiving liarozole 75 mg and 150 mg daily. In males, the serum luteinizing hormone and testosterone levels rose significantly in all the active treatment groups. CONCLUSIONS: The data confirm that liarozole is an effective treatment for psoriasis and indicate that the lowest effective dose is 75 mg twice daily. The drug seems generally to be well tolerated.

Administration, Oral↗
PubMed1998

T-cell-mediated cytotoxicity against keratinocytes in sulfamethoxazol-induced skin reaction.

BACKGROUND: The incidence of skin rashes or erythema multiforme to sulfamethoxazole in exposed patients is about 3%. Among patients with acquired immunodeficiency syndrome the risk is approximately 10 times higher. The pathogenesis of these reactions and the reason for the increased frequency in HIV infections are not understood. OBJECTIVE: To investigate drug specific T-cell-mediated cytotoxicity in sulfamethoxazole- induced skin reactions. METHODS: Specific T-cell lines and T-cell clones generated from a donor who developed a skin rash to sulfamethoxazole were assessed with a standard 4 h 51Cr cytotoxicity assay in the presence or absence of soluble sulfamethoxazole. B lymphoblasts and keratinocytes with and without interferon gamma pretreatment were used as target cells. Selective blockers of FasL/Fas and perforin-mediated killing and immunostaining for perforin were used to evaluate the involvement of the different cytolytic pathways. RESULTS: CD4+ and CD8+ sulfamethoxazole specific T-cell clones showed a drug-specific and MHC-restricted cytotoxicity against autologous B lymphoblasts in the presence of soluble sulfamethoxazole. Keratinocytes, if pretreated with interferon gamma, were specifically killed predominantly by CD4+ T-cell clones. Specific T-cell clones of both CD4+ and CD8+ phenotype showed a strong immunoreactivity for perforin and the cytotoxicity was blocked by concanamycin A which suggests a perforin-mediated killing. CONCLUSION: Perforin-mediated killing of autologous keratinocytes in the presence of soluble sulfamethoxazole by drug-specific CD4+ lymphocytes may be a pathway for generalized drug-induced delayed skin reactions. The requirement of interferon gamma pretreatment of keratinocytes for efficient specific killing might explain the increased frequency of drug allergies in generalized viral infections like HIV, when interferon gamma levels are elevated.

CD4-Positive T-Lymphocytes↗
PubMed2000

Herpes simplex virus type 1 as a cause of widespread intracorneal blistering of the lower limbs.

Herpes simplex virus (HSV) infections often manifest as acute self-limiting eruptions of grouped vesicles, which have a tendency to recur. Common manifestations include that of gingivostomatitis, vulvovaginitis, recurrent erythema multiforme, herpetic whitlow, and eczema herpeticum. We report a case of HSV-1 presenting as a symmetrical intracorneal blistering eruption involving the lower limbs in a patient with no previous history of herpes simplex infection.

Blister↗
PubMed2002

Acute generalized Hailey-Hailey disease.

A patient with extensive histologically proven Hailey-Hailey disease is described whose initial clinical presentation was suggestive of erythema multiforme or toxic epidermal necrolysis. This potentially misleading morphology of acute proven Hailey-Hailey disease has not been described previously and may be a consequence of bacterial infection exacerbating acantholysis.

Acute Disease↗
PubMed2002

Psoriasis bullosa acquisita.

We report a 51-year-old man with a 20-year history of chronic plaque psoriasis who developed an autoimmune subepidermal blistering eruption that had clinical features of bullous pemphigoid, erythema multiforme and epidermolysis bullosa acquisita. Investigations revealed a 1 : 400 titre circulating and in vivo bound IgG autoantibody that mapped to the dermal side of 1 m NaCl-split skin and localized to the lower lamina lucida/upper lamina densa on immunogold electron microscopy. Immunoblotting, using dermal extracts, showed serum binding to antigens of approximately 200- and approximately 260 kDa. Indirect immunofluorescence microscopy, using the patient's serum on archival skin sections taken from selected individuals with different forms of inherited epidermolysis bullosa as substrate, showed normal basement membrane labelling on all samples apart from recessive dystrophic epidermolysis bullosa skin (with inherent mutations in the type VII collagen gene): in these cases there was a complete absence of immunostaining. Clinically, the patient responded rapidly to combination treatment with intravenous immunoglobulin and oral corticosteroids, dapsone and mycophenolate mofetil. Autoimmune subepidermal blistering has been reported in other patients with psoriasis, although no specific target antigen has ever been determined. Our study provides preliminary evidence that, for this patient at least, the autoantibody may be targeted against a skin component closely associated with type VII collagen (the epidermolysis bullosa acquisita antigen). Therefore, we propose the term 'psoriasis bullosa acquisita' for this and possibly other patients with similar skin eruptions.

Autoimmune Diseases↗
PubMed2002

Putative drug-related pemphigus foliaceus in four dogs.

Four dogs developed cutaneous lesions following the administration of various antibiotics. Histopathology of the lesions was compatible with pemphigus foliaceus, although apoptotic cells suggestive of erythema multiforme were seen in two cases. In two dogs the lesions resolved after 7.5-8.5 months of immune-suppressive treatment. No recurrence was seen during the follow-up period (3 and 4.5 years). The lesions in the other two dogs resolved within 3 weeks to 3 months following discontinuation of the antibiotic. No recurrence of clinical signs occurred during the follow-up period (1 and 4 years, respectively).

Animals↗
PubMedDate not supplied

Adverse reaction to prednisone in a patient with systemic lupus erythematosus.

Oral corticosteroids are the main therapeutic choice for systemic lupus erythematosus (SLE). Adverse reactions to systemic corticosteroids rarely occur and the etiology is unclear in most cases. A 14-year-old girl with newly diagnosed SLE developed a pruritic bullous eruption while on prednisone. The patient had been treated successfully in the hospital with intravenous methylprednisolone. In preparation for discharge, the steroid preparation was changed to prednisone to which the patient reacted with a development of new crops of bullous lesions. Skin biopsy specimens of lesional areas showed a bullous eruption consistent with erythema multiforme. The patient underwent immediate and delayed hypersensitivity tests. Intradermal and patch tests to liquid prednisone were positive. The patient was discharged on oral methylprednisolone and has not had recurrence of the skin lesions. In conclusion, a case of prednisone sensitivity in a patient with SLE is presented here. An alternative preparation, methylprednisolone, was used to successfully treat her underlying condition.

Adolescent↗