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Demonstration of tissue 90 kD glycoprotein as antigen in circulating IgG immune complexes in dermatitis herpetiformis and coeliac disease.

Mannose-rich 90 kD glycoprotein, a constituent of skin and small-bowel mucosa, was identified as antigen in circulating IgG-type immune complexes in dermatitis herpetiformis and coeliac disease by means of an enzyme-linked immunosorbent assay. High levels of 90 kD glycoprotein-IgG complexes were found in 7 out of 12 patients with dermatitis herpetiformis and in 10 out of 20 patients with coeliac disease but in only 2 out of 20 patients with systemic lupus erythematosus. The highest levels of 90 kD antigen-IgG complexes were found in patients with dermatitis herpetiformis. The amount of these complexes did not correlate with the degree of jejunal villous atrophy. The 90 kD glycoprotein-containing immune complexes with targets in skin and gut may be involved in the pathogenesis of dermatitis herpetiformis and coeliac disease.

Adult↗

[Dermatitis artefacta: retrospective study in 31 patients].

BACKGROUND: The outcome for patients with dermatitis artefacta is not well known. The primary objective of this single-centre retrospective study was to describe the initial clinical aspects and the prognosis of the disease. The secondary objective was to describe the somatic and psychological management and long-term treatment of these patients. PATIENTS AND METHODS: Records of patients with dermatitis artefacta followed in the dermatology department over the 15 last years were reviewed independently by 2 dermatologists. Diagnostic criteria consisted of evocative clinical pictures and the exclusion of other forms of dermatosis. Data collection included: file analysis, photographs, review questionnaires sent to general practitioner or completed during a phone call to patients (follow-up data). RESULTS: Thirty-one patient files were selected: 23 women and 8 men, mean age 31 years (SD = 14.8). Clinical aspects included: erythema (50%), ulceration (37%), crust (23%) and blisters (17%). The main sites were the face (67%) and arms (43%). Topical treatment was prescribed in all cases and systemic treatment was prescribed in 23% of cases. Psychological support was offered to 65% of the patients and was accepted by 50%. A follow-up study was performed for 17 patients and showed serious complications in 4 cases consisting of psychosis (n=2) and/or severe self-mutilation (n=3) occurring over several years following diagnosis (5 years for one patient and 12 years for 2 patients). DISCUSSION: The results confirm the usual and characteristics of dermatitis artefacta such as predominance in young female patients, with lesions affecting visible areas (face, upper legs). In contrastwith published studies, no cases of attempted suicide were observed in our series, although severe dermatitis artefacta was evidenced in only a minority of patients.

Adult↗

T-helper 1, T-helper 2 and immunosuppressive cytokines in canine atopic dermatitis.

Atopic dermatitis is a common inflammatory skin disease of humans and dogs. Human atopic dermatitis is associated with T-helper (Th) 2 type responses, although Th1 cytokines are present in chronic lesions. This study used semi-quantitative reverse transcriptase polymerase chain reactions to determine the expression of gene transcripts for immunosuppressive cytokines (transforming growth factor beta [TGFbeta] and interleukin [IL]-10), Th2 type cytokines (IL-4 and IL-6) and Th1 type cytokines (interferon gamma [IFNgamma], tumour necrosis factor alpha [TNFalpha], IL-2 and IL-12) in lesional atopic, non-lesional atopic and healthy canine skin. Canine atopic dermatitis was associated with over-expression of IL-4 mRNA and reduced transcription of TGFbeta compared to healthy skin (ANOVA, p<0.05). Higher levels of IFNgamma, TNFalpha and IL-2 mRNA were seen in lesional compared to non-lesional and healthy skin (p<0.05). There were no significant differences in IL-10, IL-6 or IL-12 transcription. This is the first report to demonstrate that canine atopic dermatitis is associated with over-production of IL-4 and under expression of TGFbeta.

Animals↗

Auto IgG anti-IgE and IgG x IgE immune complex presence and effects on ELISA-based quantitation of IgE in canine atopic dermatitis, demodectic acariasis and helminthiasis.

Atopic dermatitis is a common allergic disease manifestation in dogs; however, there is no correlation between clinical disease and detectable total serum IgE. Auto antibodies of the IgG subclass against IgE may affect the detection of serum IgE by immunoassay and may be important in the regulation of IgE production by B cells. ELISA were developed to detect serum antibodies specific for IgE using a newly available canine monoclonal IgE of known antigen specificity, generated from a canine x murine heterohybridoma. To test for correlation of auto IgG anti-IgE levels with manifestation of atopic dermatitis, the sera from 101 atopic dogs were compared with sera from non-atopic dogs of various breeds, foxhounds manifesting clinical signs of demodectic acariasis and helminth parasitized random bred dogs for quantities of IgG anti-IgE measured in units/ml compared to a high titer standard serum. To test for serum effects on quantitation of IgE, known amounts of canine monoclonal IgE were added to various sera and measured by capture ELISA with detecting monoclonal antibodies specific for heat labile or heat stabile epitopes. Unheated sera from dogs manifesting clinical atopic dermatitis and helminth parasitized dogs had levels of IgG anti-IgE that were significantly lower than various breeds of dogs not manifesting dermatologic lesions and foxhounds manifesting demodectic acariasis. Heating sera at 56 degrees C for 3 h to denature the high affinity binding site on the IgE heavy chain caused a marked increase over non-heated sera in detectable IgG anti-IgE in almost all dogs. This increase was most profound in helminth-infected dogs and foxhounds manifesting demodectic mange with 7 fold increases each, respectively, and in atopic dogs with a 5 fold increase compared to 3 fold increases for clinically-normal springer spaniels and all soft coated wheaten terriers. The terriers demonstrated an association of lower heated serum values of IgG anti-IgE with manifestation of a familial syndrome of protein-losing enteropathy and protein-losing nephropathy. The ability of mouse anti-canine IgE monoclonal antibodies specific for either heat labile or heat stabile epitopes to detect canine monoclonal IgE added to sera in known amounts varied from serum to serum and at different concentrations of the same serum, but did not correlate with IgG anti-IgE values for these sera. The range of absolute levels of serum IgE in dogs showing little or no inhibition of detection of added IgE was < 0.5 ng/micromilligram to 2 micrograms/micromilligram. It was concluded that the increase in detectable IgG anti-IgE after heating sera indicates that IgG x IgE immune complexes are normally present in most dogs; however, the increase over uncomplexed IgG anti-IgE was most pronounced in dogs manifesting atopic dermatitis and demodectic acariasis. A quantitative comparison of IgG anti-IgE or IgG x IgE to total serum IgE was not made because the ability of monoclonal antibodies specific for either heat labile or heat stable epitopes on the IgE heavy chain to detect IgE added to serum, as well as innate serum IgE, was highly variable in different dilutions of serum from individual to individual.

Animals↗

Canine atopic dermatitis in Greece: clinical observations and the prevalence of positive intradermal test reactions in 91 spontaneous cases.

Atopic dermatitis was diagnosed in a total of 91 dogs by combining the compatible historical evidence and clinical signs with the presence of one or more positive intradermal test reactions well correlated with the exposure to the aeroallergens and the seasonality of the clinical signs. Compared to the general hospital population Yorkshire terriers, Chinese Shar-Peis and cocker spaniels showed a strong predilection. No such predilection was found regarding the sex of the animals. The age of the dogs at the onset of the clinical signs ranged from 2 months to 8 years (median: 2.5 years). Moderate to severe pruritus, noticed in all the 91 dogs, was either localized (29/91) or generalized (64/91) and non-seasonal (43/91), seasonal (19/91) or of unknown seasonality (29/91). The most common cutaneous lesions included erythema, hyperpigmentation, hypotrichosis and crusts; their body distribution was generalized (64%) or localized (36%) with the feet as the most common site of involvement. Five dogs that had unlesional skin were significantly younger and had been pruritic for a shorter period of time compared to the majority of our study population. Otitis externa (43/91) and bacterial pyoderma (30/91) were the most common conditions associated with atopic dermatitis, while the prevalence of Malassezia dermatitis was very low (2/91). Of the other allergic skin diseases flea allergic dermatitis was the most common (29/91) followed by food hypersensitivity (2 out of the 15 dogs tested). The majority of the dogs demonstrated multiple sensitivities to the 50 aeroallergens tested, while domestic mites (77/91), and particularly Dermatophagoides farinae (64/91), were the most commonly implicated. The total number of the positive intradermal test reactions was increasing parallel to the age of the dogs but it was negatively associated with the presence of skin lesions on the carpal and tarsal joints.

Animals↗

Long-term efficacy of medium-dose UVA1 phototherapy in atopic dermatitis.

BACKGROUND: UVA1 (340-400 nm) therapy proved to be highly effective in patients with severe atopic dermatitis. The optimal dose regarding therapeutic efficacy and possible side effects is still to be evaluated. In vitro cell culture as well as in vivo animal studies recently indicated that a correlation between UVA irradiation and photoaging, skin carcinogenesis, or melanoma induction may exist. Therefore it seems appropriate to focus research activities on reducing the UVA1 dose applied during phototherapeutic regimens minimizing nonbeneficial side effects. OBJECTIVE: The present study was performed to evaluate the therapeutic effectiveness and long-term efficacy of medium-dose UVA1 irradiation in patients treated for acute exacerbated atopic dermatitis. METHODS: Thirty-two patients underwent a medium-dose UVA1 therapy consisting of 15 treatments applied from Monday to Friday for a period of 3 weeks. The applied dose per treatment was 50 J/cm(2) resulting in a cumulative dose of 750 J/cm(2). Clinical severity was assessed according to the SCORAD index before and after irradiation as well as in monthly intervals up to 3 months after cessation of phototherapy. RESULTS: Medium-dose UVA1 phototherapy is effective for alleviating acute exacerbated atopic dermatitis as shown by a significant reduction of SCORAD ratings (P <.001) at the end of the active UV treatment period. A significant skin improvement was still present 1 month later (P <.001). However, at the end of the 3-month posttreatment observation period the skin condition had reached the pretreatment level. CONCLUSION: According to our data, medium-dose UVA1 phototherapy is a highly effective, nonsteroidal, therapeutic alternative for treatment of acute exacerbated atopic dermatitis. However, effectiveness is merely short term, limited, and is followed by recurrence of symptoms within a 3-month observation interval.

Adolescent↗

Seborrheic dermatitis in patients with acquired immunodeficiency syndrome.

Many cutaneous disorders are associated with acquired immunodeficiency syndrome. We prospectively evaluated eighteen patients with acquired immunodeficiency syndrome and twelve patients with the immunodeficiency syndrome-related complex for dermatologic disorders. A high prevalence of seborrheic dermatitis was found in patients with acquired immunodeficiency syndrome--83%, in comparison with 1% to 3% of historic control subjects. Patients with the related complex also had an increased incidence of 42%. Seborrheic dermatitis in this population was often more explosive, inflammatory, and severe than is usually seen in otherwise healthy patients. Severity of seborrheic dermatitis correlated with a poor overall prognosis in our patients. Additionally, seborrheic dermatitis may be one of the most common cutaneous manifestations of acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗

Seborrheic-like dermatitis of acquired immunodeficiency syndrome. A clinicopathologic study.

We studied twenty-five skin biopsies from twenty-one patients with acquired immunodeficiency syndrome or its prodrome who presented with the "seborrheic dermatitis" associated with acquired immunodeficiency syndrome and compared them with an equal number of biopsies from patients with seborrheic dermatitis who had neither acquired immunodeficiency syndrome nor its risk factors. We found that although the eruption in acquired immunodeficiency syndrome closely resembles seborrheic dermatitis, histologically it is distinctive because it shows spotty keratinocytic necrosis, leukoexocytosis, and a superficial perivascular infiltrate of plasma cells and, frequently, neutrophils that show occasional leukocytoclasis. In long-standing lesions, hyperkeratosis is often present. None of these histologic features are commonly encountered in seborrheic dermatitis, psoriasis, or other eruptions known to us.

Acquired Immunodeficiency Syndrome↗

Sensitivity and specificity of IgA-class antiendomysial antibodies for dermatitis herpetiformis and findings relevant to their pathogenic significance.

The specificity and sensitivity of the recently reported IgA-class antiendomysial antibody test for gluten-sensitive enteropathy were evaluated in four double-blind studies involving the sera of fifty-seven patients with dermatitis herpetiformis who were not on a gluten-free diet and ninety-seven assorted control sera. The control sera provided by the four centers included the sera of nineteen patients with dermatitis herpetiformis and two with celiac disease who were on a gluten-free diet, the sera of five normal subjects with human lymphocyte antigens (B8 locus), the sera of thirteen patients with linear IgA bullous dermatosis, and fifty-eight other control sera, mostly from patients with other bullous diseases and other dermatoses. The frequency of IgA antiendomysial antibody in these coded studies was zero of ninety-seven control sera and thirty-four of fifty-seven sera (60%) from patients with dermatitis herpetiformis who were not on a gluten-free diet. The pathogenic role of IgA antiendomysial antibodies in dermatitis herpetiformis and celiac disease is suggested not only by their high degree of disease sensitivity and specificity but also by their formation in response to gluten challenge, their appearance before gut changes, and the in vitro binding of gliadin to the antiendomysial antibody antigen sites. These and other findings in this study and in the literature suggest that gluten-sensitive enteropathy is immunologically mediated and that IgA antiendomysial antibodies play a significant pathogenetic role.

Animals↗

Diet and atopic dermatitis.

Prevention or modification of the onset of atopic dermatitis has been difficult to document through prolonged breast feeding or delayed introduction of solid foods. Dietary management of established atopic dermatitis is not routinely indicated for the majority of patients. Dietary management of atopic dermatitis should not be continued indefinitely. Gradual reintroduction of the offending food(s) is often appropriate. The foods most commonly avoided in the management of atopic dermatitis are cow's milk, wheat, eggs, and nuts. Severe or prolonged dietary restrictions should not be instituted without full consideration of their impact on the patient's general health.

Age Factors↗

Interface dermatitis in patients with the acquired immunodeficiency syndrome.

We report twenty-five patients with the acquired immunodeficiency syndrome (AIDS) and interface dermatitis. Patients with AIDS and interface dermatitis had numerous opportunistic and herpetic infections. Nearly all patients were receiving at least one medication prior to the development of their rash and many were clinically thought to have a drug eruption. When compared to skin biopsy specimens from non-AIDS patients with drug eruptions, specimens from patients with AIDS and interface dermatitis demonstrated a greater degree of vacuolar change, the frequent occurrence of necrotic keratinocytes, often in clumps, and the absence of eosinophils and polymorphonuclear leukocytes in the dermal infiltrates. Histologic and clinical features of our patients with AIDS and interface dermatitis are presented and contrasted with other interface dermatitides. Systemic and cutaneous immune abnormalities in patients with AIDS may be relevant to the pathogenesis of this interface process.

Acquired Immunodeficiency Syndrome↗

Milk tester's dermatitis.

Hand dermatitis is a frequent problem among workers in milk testing laboratories. An epidemiologic study was conducted at the Pennsylvania Dairy Herd Improvement Association Milk Testing Laboratory, where more than 300,000 milk samples are examined monthly for protein, butterfat, and "somatic" cells. These samples are preserved with potassium dichromate for transport from the farm to the laboratory. A survey of the laboratory was conducted and workers were interviewed. Eight of 16 subjects reported a history of occupationally exacerbated hand dermatitis. Three of 16 subjects had positive patch test results to potassium dichromate. Two of 15 subjects who underwent patch testing to milk preserved with potassium dichromate had positive reactions. None reacted to milk alone, bronopol, or Kathon CG. Two workers are receiving workers' compensation because of severe allergic contact dermatitis of the hands to potassium dichromate. We conclude that milk testing laboratory workers are at substantial risk for acquiring allergic contact dermatitis from milk preserved with potassium dichromate.

Animals↗

Association of Pityrosporum orbiculare (Malassezia furfur) with seborrheic dermatitis in patients with acquired immunodeficiency syndrome (AIDS).

The possible causative role of the yeastlike fungus Pityrosporum (Malassezia) orbiculare in the pathogenesis of seborrheic dermatitis in patients with and without acquired immunodeficiency syndrome (AIDS) has been discussed but not resolved. Ten patients with AIDS-related seborrheic dermatitis were studied for the presence of Pityrosporum organisms. On the basis of a quantitative correlation between numbers of yeast cells adherent to and extruded from keratinocytes and the clinical severity of seborrheic dermatitis, an association, if not a causative role, for Pityrosporum is strongly suggested in seborrheic dermatitis in patients with AIDS. This association was further strengthened by the marked clinical response to ketoconazole in two patients with a concomitant decrease in the number of Pityrosporum cells per keratinocyte.

Acquired Immunodeficiency Syndrome↗

Response of mononuclear leukocyte cyclic adenosine monophosphate-phosphodiesterase activity to treatment with topical fluorinated steroid ointment in atopic dermatitis.

Our studies of mononuclear leukocyte peripheral blood homogenates demonstrate significantly increased cyclic adenosine monophosphate-specific phosphodiesterase activity in patients with atopic dermatitis who were untreated for 1 week, compared with normal adult nonatopic control subjects. Phosphodiesterase activity is not related to the extent or activity of the patient's disease or the presence or absence of allergic respiratory disease. Enzyme kinetic studies showed a triphasic plot in normal mononuclear leukocytes but a biphasic plot in atopic dermatitis. This may be interpreted as an absence of an enzyme with a low (0.080) Michaelis Menton constant (Km) in atopic dermatitis samples. One week of therapy with a topical fluorinated steroid ointment caused a significant reduction in disease activity. Although a slight reduction in mean total phosphodiesterase activity occurred, it did not reach statistical significance. One week's treatment, however, caused the abnormal biphasic kinetic plot to revert to a triphasic plot with return of the low Km enzyme form in those patients who showed a fall in phosphodiesterase activity. This finding suggests that the elevated phosphodiesterase activity in atopic dermatitis may be responsive in a limited degree to topical steroid therapy.

3',5'-Cyclic-AMP Phosphodiesterases↗

A double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of thymopentin as an adjunctive treatment in atopic dermatitis.

BACKGROUND: Multiple immunologic abnormalities such as impaired T-cell function, elevated serum IgE level, and increased interleukin 4 production have been demonstrated in patients with atopic dermatitis. OBJECTIVE: As part of a 12-week, multicenter, double-blind, placebo-controlled clinical trial, we evaluated the safety and efficacy of thymopentin (Timunox) as an adjunctive treatment in patients with severe atopic dermatitis. METHODS: Thirty-nine patients at least 2 years old with severe atopic dermatitis on a minimum of 20% of their cutaneous surface area were randomly selected to receive either thrice-weekly subcutaneous injections of thymopentin, 50 mg, or placebo. Use of triamcinolone 0.1% or hydrocortisone 1.0% cream and oral antihistamines were permitted during this trial. RESULTS: After 12 weeks, thymopentin-treated patients had significantly greater improvement than those receiving placebo. No thymopentin-related adverse events occurred. CONCLUSION: Thymopentin may be a safe effective adjunct to therapy in patients with severe atopic dermatitis.

Adolescent↗

Relief of pruritus in patients with atopic dermatitis after treatment with topical doxepin cream. The Doxepin Study Group.

BACKGROUND: Atopic dermatitis is associated with severe pruritus for which effective topical treatment is lacking. As a potent H1 and H2 antagonist, the antipruritic effect of topical doxepin was first demonstrated in histamine-induced itch in nonatopic volunteers. OBJECTIVE: The current study was undertaken to compare the efficacy and safety of topical 5% doxepin cream in relieving pruritus associated with atopic dermatitis. METHODS: A total of 270 patients with atopic dermatitis who had daily moderate to severe pruritus for at least 1 week were enrolled in the double-blind, vehicle-controlled, multicenter study. Treatment was randomly assigned: 5% doxepin cream or vehicle cream was applied twice on the day of the baseline visit and four times daily for the remainder of the 7-day trial. RESULTS: Relief of pruritus was achieved in 85% of doxepin-treated patients and 57% of vehicle-treated patients by day 7; a majority of these positive responses occurred during the first 24 hours. Pruritus severity scores demonstrated significantly greater improvement with topical doxepin at each study visit (p < 0.01). Visual analogue scales for pruritus severity and pruritus relief showed similar improvement in the doxepin-treated group. At each of three visits, the physician's global evaluation for relief of pruritus also showed significant improvement in the doxepin treatment group (p < 0.01). The physician's global evaluations of eczema significantly favored topical doxepin on day 7 (p < 0.01). Nineteen patients withdrew from the study because of adverse effects (doxepin, n = 16; vehicle, n = 3). The most commonly reported were localized stinging or burning (doxepin group, n = 39; vehicle group, n = 34) and drowsiness (doxepin group, n = 37; vehicle group, n = 3), all of which decreased in frequency and severity over time. CONCLUSION: Topical doxepin is effective in reducing pruritus in patients with atopic dermatitis. It has an apparent short-term low risk of major side effects or sensitization.

Administration, Cutaneous↗

The occurrence of atopic dermatitis in north Europe: an international questionnaire study.

BACKGROUND: Atopic dermatitis is a common multifactorial disease that seems to be increasing in frequency. OBJECTIVE: Our purpose was to determine the increased prevalence of atopic dermatitis in North Europe. METHODS: Approximately 3000 7-year-old children in Denmark, Germany, and Sweden were enrolled in a cross-sectional questionnaire study that was conducted in the autumn of 1992 with common protocols and standardized procedures. RESULTS: The response rate was 90%. The frequency of atopic dermatitis was calculated to be 15.6% (95% confidence interval 14.2% to 17%) with some regional differences. Girls more often had flexural eczema and outnumbered boys in a ratio of 1.3:1.0. Boys more often had a personal history of asthma, whereas girls more often had a family history of asthma. CONCLUSION: The increasing prevalence of atopic dermatitis has been confirmed. This simple questionnaire model works well, is cost effective, and is sufficiently sensitive and specific to conduct large-scale epidemiologic investigations in school children.

Asthma↗

Papular dermatitis (subacute prurigo, "itchy red bump" disease): pilot study of phototherapy.

BACKGROUND: Some patients with a subacute or chronic pruritic erythematous papular eruption are refractory to treatment. We previously described a number of these patients with papular dermatitis or subacute prurigo. OBJECTIVE: The purpose of this study was to examine the effectiveness of different types of phototherapy for treatment of papular dermatitis. METHODS: We reviewed the medical records of 11 patients who were diagnosed with papular dermatitis and who underwent phototherapy within the last 5 years. RESULTS: Eleven patients had a total of 17 phototherapy courses: psoralen-UVA (PUVA; 9), UVA/UVB light (3), and UVB alone (5). Within the PUVA treatment group, three of nine patients experienced total clearing, and six of nine patients experienced partial improvement. Although patients in all groups relapsed with time, overall the PUVA-treated patients had the best response rate and the best chance of the condition remaining clear after treatment was stopped. CONCLUSION: PUVA may be an effective treatment for papular dermatitis. The frequency of relapse indicates that maintenance treatments may be necessary for long-term control of the disease.

Aged↗