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Cinnamon-induced oral erythema multiformelike sensitivity reaction.

BACKGROUND: Erythema multiforme, or EM, is a hypersensitivity reaction to agents such as herpes virus, drugs or foods. Oral EM-like reactions may be induced by cinnamon. It is important for dentists to recognize this condition. CASE DESCRIPTION: The authors report an unusual case of cinnamon-induced oral EM-like reaction in an older female patient. The disease manifested itself as chronic extensive surface ulcerations and lip swelling. The patient was treated repeatedly with topical and systemic steroids but responded to them only temporarily. The patient was cured when the offending agent--cinnamon--was eliminated from her diet. CLINICAL IMPLICATIONS: Oral EM or EM-like reactions pose a diagnostic dilemma due to their varied etiologies and clinical manifestations. Correct diagnosis is essential for effective treatment. A negative skin test does not rule out an allergic reaction to food.

Administration, Topical↗

First cases of animal diseases published since 2000. 1. Dogs.

In this first article of a series of papers listing first case reports of animal diseases published since 2000, the following 19 cases of dog diseases are discussed: Blastomycotic granuloma involving the cranial vena cava. Congenital myocardial hamartoma. Discospondylitis: three cases caused respectively by Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus epidermidis. Dystrophin deficient muscular dystrophy in a Labrador Retriever. Emphysematous prostatitis. Erythema multiforme major caused by a Parvovirus infection of keratinocytes. Hemochromatosis due to repeated blood transfusions. Intraspinal synovial cyst. Juvenile nephropathy in the Collie and the Irish Wolfhound. Primary cerebellar cortical degeneration (abiotrophy) in a Scottish terrier. Primary pulmonary artery chondrosarcoma. Renal dysplasia in a Bull Mastiff. Rhabdomyosarcoma (botryoid sarcoma) of the urinary bladder in a Maltese. Spinal mast cell tumor. Spongiform degeneration of the white matter in the central nervous system of Australian Cattle dog. Systemic pasteurellosis caused by Pasteurella canis. Thymic hemorrhage caused by dicumarol intoxication. Undimerized biclonal gammopathy with a single heavy chain class IgA in a dog with multiple myeloma. After a short introduction, the bibliographical data and the abstract of the author(s) and mostly some additional information derived from the article are given. The article will be regularly updated adding overlooked as well as new first reports.

Animals↗

Acute episodic inflammatory lesions of the mucous membrane and skin.

The first consideration in the treatment of erythema multiforme is to search for and eliminate a possible underlying cause. Mild cases require little treatment. Severe forms of the disease must receive prompt, active therapeutic measures. Fluid and electrolyte imbalance must be corrected, secondary bacterial infections must be combated with topical or systemic antibiotics, and large doses of systemic corticosteroids are used for short periods. Without treatment, lesions can persist for many weeks. Mild forms of the disease, which constitute most of the cases, usually subside in a few days to two to three weeks without sequelae. Severe forms persist for three to six weeks longer; sequelae include neurologic changes, corneal opacities, blindness, conjunctival, vaginal, or preputial synechiae, and esophageal strictures. Mortality of all forms has been reported as less than 0.5% but severe cases, at approximately 10%. Recurrences are likely in approximately 25% of the cases; the pattern is variable, chronic, and episodic.

Adult↗

Clinical pattern of cutaneous drug eruption among children and adolescents in north India.

Various types of cutaneous drug eruptions and the incriminating drugs were analyzed in 50 children and adolescents up to 18 years of age (34 or 65% boys, 16 or 32% girls). Thirteen (26%) patients had a maculopapular rash, 11 (22%) a fixed drug eruption (FDE), 10 erythema multiforme (EM), 6 (12%) toxic epidermal necrolysis (TEN), 5 (10%) Stevens-Johnson syndrome (SJS), 3 (6%) urticaria, and 2 (4%) erythroderma. The incubation period for maculopapular rashes, SJS and TEN due to commonly used antibiotics and sulfonamides was short, a few hours to two to three days, reflecting reexposure, and for drugs used sparingly such as antiepileptics and antituberculosis agents, was approximately one week or more, suggesting a first exposure. Antibiotics were responsible for cutaneous eruptions in 27 patients, followed by antiepileptics in 17, analgin in 4, and metronidazole and albendazole in 1 each. Cotrimoxazole, a combination of sulfamethoxazole and trimethoprim, was the most common antibacterial responsible for eruptions (11 patients), followed by penicillin and its semisynthetic derivatives (8 patients), sulfonamide alone (3 patients), and other antibiotics (4 patients). Antiepileptics were the most frequently incriminated drugs in EM, TEN, and SJS. The role of systemic corticosteroids in the management of SJS and TEN is controversial. We administered prednisolone or an equivalent corticosteroid 2 mg/kg/day for 7 to 14 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Assessment and management of cutaneous reactions with amifostine administration: findings of the ethyol (amifostine) cutaneous treatment advisory panel (ECTAP).

PURPOSE: To review reports of severe skin reactions during amifostine treatment. METHODS AND MATERIAL: The expert panel reviewed postmarketing reports of skin reactions and discussed strategies for evaluation and management. RESULTS: Between 1994 and April 2002, 35 events were classified as severe skin reactions worldwide: erythema multiforme (8), Stevens-Johnson syndrome (10), toxic epidermal necrolysis (11), toxicoderma (3), and bullae (3). Unadjusted incidences were 6-9 per 10,000 radiotherapy patients and 0.8-1 per 10,000 chemotherapy patients. In 10 patients (29%) amifostine was continued after cutaneous signs and symptoms appeared. CONCLUSIONS: Practical recommendations for practicing clinicians were developed. Cutaneous evaluation for rash, ulceration, or lesions-particularly on lips/mucosa, palmar/plantar surfaces, and the trunk-should be performed before amifostine administration. Reactions can be classified as local injection site/radiation port reactions or non-injection site reactions; and non-injection site reactions with associated fever or constitutional symptoms must be differentiated from radiation-induced dermatitis or cutaneous reaction with another etiology. Amifostine should be permanently discontinued for severe skin reactions or reactions associated with constitutional symptoms not known to be due to any other etiology. Increased physician awareness, proper patient management, monitoring before administration, and early intervention/discontinuation for non-injection site reactions may reduce the incidence of cutaneous reactions and enhance amifostine safety.

Adolescent↗

[Autoimmune bullous skin diseases].

INTRODUCTION: Important advances have been made in the pathogenesis of autoimmune bullous skin diseases during the last 10 years. The aim of this review is to describe new types of autoimmune bullous skin diseases and to summarize progresses in the pathogenesis and treatment of these diseases. CURRENT KNOWLEDGE AND KEY POINTS: Paraneoplastic pemphigus (PNP) is a new type of pemphigus, distinct from pemphigus vulgaris (PV) and pemphigus foliaceus (PF). It has both clinical and histological features of pemphigus, bullous pemphigoid (BP), erythema multiforme, and lichen planus, in patients with lymphoma. Numerous clinical types of autoimmune bullous skin diseases of the dermal epidermal junction have also been described. Analysis of patients' serum by immunoblotting and immunoprecipitation allowed the identification of target antigens of most of these diseases: PV and PF are due to the production of autoantibodies directed against adhesion molecules (desmoglein 1 and 3) that belong to the cadherin family. In PNP, autoantibodies are directed against plakins, a new family of desmosomal plaque proteins. BP, CP and pemphigoid gestationis are characterized by the production of autoantibodies mainly directed against two hemidesmosomal proteins: BPAG1 and BPAG2. The mortality rate of autoimmune bullous skin diseases is estimated between 10 and 40%, mainly due to infections and cardiovascular diseases. The potential interest of the first use of adjuvant therapies in addition to corticosteroids has not been demonstrated yet. FUTURE PROSPECTS AND PROJECTS: Due to the numerous side-effects of oral corticosteroids, many therapeutic trials are aimed at finding other treatments for the management of these diseases. Topical corticosteroids could be effective in BP, and even in some cases of pemphigus. New treatments using specific immunoadsorption of pathogenic autoantibodies with recombinant proteins will probably be available in the future.

Autoantibodies↗

Enzyme-linked immunosorbent assay for detection of peptide-specific human antidesmoplakin autoantibodies.

BACKGROUND: Autoantibodies directed against desmoplakin (Dp) I and II have recently been characterized in a subset of patients with severe erythema multiforme (EM), a recurrent inflammatory skin disease with a broad spectrum of clinical manifestations. These autoantibodies recognize a peptide epitope localized within the extreme end of the carboxy terminal domain of Dp responsible for the assembly of keratin filaments to the desmosomal plaque. Using dot blot analysis with overlapping synthetic peptides, the binding epitope YSYSYS has been identified. OBJECTIVES: To establish an enzyme-linked immunosorbent assay (ELISA) for detection of peptide-specific anti-Dp autoantibodies in sera of patients with EM. METHODS: A synthetic peptide containing the respective amino acid sequence was used as matrix for ELISA plates. Serum samples from patients with known EM and peptide-specific anti-Dp autoantibodies verified by immunoblotting, immunoprecipitation and epitope mapping were used. RESULTS: Establishing an index value of 42.0, 25 of 25 serum samples from five patients with peptide-specific anti-Dp autoantibodies were positive in the ELISA. From control sera, none of 31 bullous disease sera and only one (1.2%) of 83 normal human sera were positive. CONCLUSIONS: These data show that the ELISA presented in this study represents a sensitive and highly specific tool for the detection of peptide-specific anti-Dp autoantibodies in patients with EM.

Autoantibodies↗

[Primary and isolated cutaneous lymphomatoid granulomatosis following heart-lung transplantation].

BACKGROUND: Lymphomatoid granulomatosis is an Epstein-Barr virus-associated B-cell lymphoproliferative disease. It is angiocentric and angiodestructive and involves the lungs, central nervous system and skin. Exclusive cutaneous involvement is rare and may be associated with a better outcome. Contrarily to the extra-cutaneous forms of lymphomatoid granulomatosis, it is difficult or impossible to detect Epstein-Barr virus DNA sequences in primary and isolated cutaneous lymphomatoid granulomatosis. CASE REPORT: A 54-year-old woman developed erythemato-violaceous lesions on both legs 3 years after a heart-lung transplantation. The diagnosis of erythema multiforme and of drug-induced vasculitis were first made. Because of fever and of the rapid extension of the lesions, the patient was hospitalized. The histologic examination of the first lesions showed a perivascular infiltrate, without epidermotropism, composed of histiocytes, lymphocytes and plasma cells. Immunohistochemistry revealed the presence of a predominantly T-cell infiltrate with some large B cells. Subsequent biopsies were diagnosed as high grade B-cell lymphoma. Polymerase chain reaction analysis as well as in situ hybridation study showed the presence of Epstein-Barr virus load in the lesions. There was however no serologic evidence of viral reactivation. Extensive systemic evaluation revealed no visceral or bone marrow involvement. Despite antiviral treatment and CHOP polychemotherapy, the patient died 3 months after her admission. DISCUSSION: This observation of lymphomatoid granulomatosis is particular because of its exclusive cutaneous involvement associated with a fulminant evolution to high grade B lymphoma. The presence of a context of iatrogenic immunosuppression underlies the role of altered immune cellular functions in the initiation and/or progression of lymphomatoid granulomatosis and strengthens the role of a viral agent in its pathogenesis. We suggest that the presence of Epstein-Barr virus, which is generally not associated with the isolated cutaneous forms of lymphomatoid granulomatosis, may have played a role in this fulminant evolution to high grade B lymphoma.

Diagnosis, Differential↗

Serum interleukin-6 level is a useful marker in evaluating therapeutic effects of levamisole and Chinese medicinal herbs on patients with oral lichen planus.

BACKGROUND: Oral lichen planus (OLP) is a T cell-mediated inflammatory disease. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that keratinocytes and tissue-infiltrating mononuclear cells from OLP lesions can secrete IL-6. In some OLP patients, the high serum IL-6 levels are reduced after treatment, suggesting that IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 180 patients with erosive OLP (EOLP), nonerosive OLP (NEOLP), erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some OLP patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5.5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that approximately 99% of the normal control subjects and the patients with EM, TU, or OSF had a normal serum IL-6 level less than 5.0 pg/ml. However, 15% (22/149) OLP patients, 15% (20/136) EOLP patients, 20% (5/25) major type EOLP patients, 14% (15/111) minor type EOLP patients, 15% (2/13) NEOLP patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum IL-6 level greater than 5.0 pg/ml. The mean serum IL-6 level in patients with OLP (3.4 +/- 3.1 pg/ml, P < 0.001), EOLP (3.4 +/- 3.2 pg/ml, P < 0.001), major type EOLP (4.9 +/- 3.5 pg/ml, P < 0.001), minor type EOLP (3.0 +/- 3.0 pg/ml, P < 0.01), or NEOLP (4.2 +/- 1.5 pg/ml, P < 0.001) was significantly higher than that in normal control subjects (2.0 +/- 1.5 pg/ml). A significant difference in the mean serum IL-6 level was also found between major type and minor type EOLP patients (P < 0.01). The mean reduction of serum IL-6 level in OLP patients treated with levamisole plus Chinese medicinal herbs was significantly higher (7.4 +/- 4.7 pg/ml) than that in OLP patients treated with levamisole only (3.8 +/- 2.3 pg/ml, P < 0.05), suggesting that the combination therapy was superior to levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in OLP patients. IL-6 may be a useful marker in evaluating therapeutic effects and in monitoring the disease status of OLP.

Adjuvants, Immunologic↗

Levamisole and Chinese medicinal herbs can modulate the serum interleukin-6 level in patients with recurrent aphthous ulcerations.

BACKGROUND: Recurrent aphthous ulcerations (RAU) are common oral inflammatory lesions. Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has effects on cellular and humoral immunities. Previous studies have shown that the high serum IL-6 levels in some RAU patients can be reduced by drug treatment. This finding suggests that IL-6 may be a useful marker in evaluating therapeutic effects of RAU. METHODS: In this study, we used a solid phase, two-site sequential chemiluminescent immunometric assay to determine the baseline serum levels of IL-6 in a group of 228 patients with RAU, erythema multiforme (EM), traumatic ulcers (TU), oral submucous fibrosis (OSF), pemphigus vulgaris (PV), or Sjögren's syndrome (SS), and in 77 normal control subjects. Some RAU patients were treated with levamisole plus Chinese medicinal herbs or levamisole only for 0.5-5 months and their serum IL-6 levels were measured after treatment. RESULTS: We found that about 99% of the normal control subjects and the patients with EM, TU, or OSF had a serum IL-6 level within the normal limit of 5.0 pg/ml. However, 24% (48/197) RAU patients, 14% (1/7) EM patients, 43% (3/7) PV patients, and 100% (6/6) SS patients had a serum level of IL-6 greater than 5.0 pg/ml. The mean serum level of IL-6 in patients with RAU (3.6 +/- 3.5 pg/ml, P < 0.001), minor type RAU (2.7 +/- 2.0 pg/ml, P < 0.05), major type RAU (5.2 +/- 4.6 pg/ml, P < 0.001), or herpetiform type RAU (4.1 +/- 3.8 pg/ml, P < 0.01) was higher than that in normal control subjects. The mean serum level of IL-6 in major type (P < 0.001) or in herpetiform type RAU patients (P < 0.05) was higher than that in minor type RAU patients. The mean reduction of serum IL-6 level (10.0 +/- 7.1 pg/ml) in RAU patients after treatment with levamisole plus Chinese medicinal herbs was significantly higher than that (5.1 +/- 3.7 pg/ml) in RAU patients after treatment with levamisole only (P < 0.005), suggesting that the combination therapy is superior to the single therapy of levamisole only. CONCLUSION: We conclude that levamisole and levamisole plus Chinese medicinal herbs can modulate the serum IL-6 level in RAU patients. Although the therapeutic effect of RAU can be assessed by a decrease in the frequency, duration and number of the oral ulcerations, it can also be monitored by a reduction of serum IL-6 level in RAU patients.

Adjuvants, Immunologic↗

In three types of interface dermatitis, different patterns of expression of intercellular adhesion molecule-1 (ICAM-1) indicate different triggers of disease.

We found distinct patterns of intercellular adhesion molecule-1 (ICAM-1) expression in three diseases characterized by interface dermatitis with mononuclear infiltrates and keratinocyte cytotoxicity: lichen planus (LP), subacute cutaneous lupus erythematosus (SCLE), and erythema multiforme (EM). In LP, basal keratinocytes show strong ICAM-1 expression associated with a dermal infiltrate, but ICAM-1 expression in the rest of the epidermis is minimal. In SCLE, there is diffuse epidermal ICAM-1 expression, sometimes with accentuation on the cell surface of basal cells. In EM, there is strong basal cell expression of ICAM-1 with evident cell surface accentuation, and also pockets of suprabasal expression with cell surface accentuation. These patterns are associated with different factors that trigger cytokine release in different locations. Both tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) produce greater relative ICAM-1 expression in basal keratinocytes than in more differentiated keratinocytes. In LP, the pure basal keratinocyte expression of ICAM-1 appears to be caused by cytokines, predominantly IFN-gamma, released by dermal lymphocytes. The pattern of ICAM-1 in SCLE corresponds to the pattern induced by ultraviolet radiation (UVR): diffuse epidermal ICAM-1 expression, sometimes with basal accentuation. Some individuals are "responders" to TNF-alpha or UVR, showing high levels of ICAM-1 expression following UVR or TNF-alpha stimulation in vitro or UVR stimulation in vivo. We propose that the pattern of ICAM-1 induction in SCLE is dependent on UVR-induced TNF-alpha release. EM is associated with apparent latent Herpes simplex virus, and Herpes simplex virus (HSV)-infected keratinocytes show enhanced ICAM-1 expression. We propose that in EM suprabasal ICAM-1 expression may be induced directly by HSV infection or indirectly through TNF-alpha release induced by HSV reactivation. Induction of ICAM-1 within the epidermis is stratified and individually variable. Basal keratinocytes show maximal induction of ICAM-1 expression due to innate sensitivity to TNF and IFN-gamma stimulation, and to location adjacent to dermal sources of cytokines. Suprabasal ICAM-1 can be induced by UVR and epidermal TNF-alpha release, and by factors such as viral infection. Different triggers of cytokine release and adhesion molecule induction may influence the different patterns of inflammation seen in diverse inflammatory skin diseases.

Erythema Multiforme↗

Cutaneous effects of the most commonly used antidepressant medication, the selective serotonin reuptake inhibitors.

Selective seritonin reuptake inhibitors (SSRIs) are widely used antidepressants that are often safer than alternatives, but may produce a variety of cutaneous reactions including spontaneous bruising, pruritus, urticaria, angioedema, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema nodosum, alopecia, hypertrichosis, leukocytoclastic vasculitis, and an acneiform eruption. We review this category of medications and its side effects. Many cutaneous alterations seen in association with SSRIs can be serious, some even life threatening. Because there appears to be cross-reactions between SSRIs, even though they have different chemical structures, it is advisable to use another family of antidepressants if an SSRI is linked with a serious skin eruption.

Antidepressive Agents↗

[Serum IgE in skin diseases of children (author's transl)].

Using the paper-radioimmunosorbens test (PRIST) normal values were obtained from 200 non-allergic children. The IgE level was aged-dependent, in part with significant differences between various age groups. These normal values were compared with those in children with seborrhoeic dermitis, constitutional neurodermatitis, parasitoses, urticaria, Quincke oedema, Schönlein-Henoch purpura, pityriasis rosea, multiform exudative erythema, erythema nodosum and infantile papular acrodermatitis. Half-life of IgE in neonates was 16.2 hours.

Acrodermatitis↗