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Leukocyte colony-stimulating factors. A review of associated neutrophilic dermatoses and vasculitides.

BACKGROUND: Hematopoietic colony-stimulating factors are a diverse group of cytokines now commercially available through recombinant technology. The colony-stimulating factors have proven utility in a wide spectrum of cytopenic states, and their use is now common-place. Unlike many cytokines, the colony-stimulating factors are usually well tolerated. We present a dramatic case of pyoderma gangrenosum arising during granulocyte colony-stimulating factor therapy. Additionally, the relevant literature regarding cutaneous complications of colony-stimulating factor therapy is summarized. OBSERVATIONS: Including our case, two reported patients developed pyoderma gangrenosum while under colony-stimulating factor therapy. Sweet's syndrome presented in an additional three patients, and necrotizing vasculitis was precipitated in three others. The eruptions consistently developed after 1 to 2 weeks of colony-stimulating factor therapy and were apparently unrelated to the underlying systemic illness. Although most reactions developed de novo, three were superimposed on a preexisting inflammatory process. CONCLUSIONS: Serious cutaneous adverse effects of colony-stimulating factors are distinctly rare but include neutrophilic dermatoses and necrotizing vasculitis. Upregulation of neutrophilic function and secondary release of cytokines may induce these complications. Early recognition and cessation of colony-stimulating factor therapy will limit the morbidity of these adverse events.

Adult↗

Induction of rosaceiform dermatitis during treatment of facial inflammatory dermatoses with tacrolimus ointment.

BACKGROUND: Tacrolimus ointment is increasingly used for anti-inflammatory treatment of sensitive areas such as the face, and recent observations indicate that the treatment is effective in steroid-aggravated rosacea and perioral dermatitis. We report on rosaceiform dermatitis as a complication of treatment with tacrolimus ointment. OBSERVATIONS: Six adult patients with inflammatory facial dermatoses were treated with tacrolimus ointment because of the ineffectiveness of standard treatments. Within 2 to 3 weeks of initially effective and well-tolerated treatment, 3 patients with a history of rosacea and 1 with a history of acne experienced sudden worsening with pustular rosaceiform lesions. Biopsy revealed an abundance of Demodex mites in 2 of these patients. In 1 patient with eyelid eczema, rosaceiform periocular dermatitis gradually appeared after 3 weeks of treatment. In 1 patient with atopic dermatitis, telangiectatic and papular rosacea insidiously appeared after 5 months of treatment. CONCLUSIONS: Our observations suggest that the spectrum of rosaceiform dermatitis as a complication of treatment with tacrolimus ointment is heterogeneous. A variety of factors, such as vasoactive properties of tacrolimus, proliferation of Demodex due to local immunosuppression, and the occlusive properties of the ointment, may be involved in the observed phenomena. Future studies are needed to identify individual risk factors.

Acne Vulgaris↗

Effective and safe use of lasers, light sources, and radiofrequency devices in the clinical management of Asian patients with selected dermatoses.

BACKGROUND AND OBJECTIVES: The use of lasers, light sources, and radiofrequency devices in Asian patients differs from their use in Caucasians in several respects. STUDY DESIGN/MATERIALS AND METHODS: The disease spectrum is very different with pigmentary disorders being more commonly encountered in Asian populations. Asian skin, with its higher epidermal melanin content, is more likely to develop adverse reactions, especially post-inflammatory hyperpigmentation (PIH), following treatment. RESULTS AND CONCLUSIONS: The purpose of this article is to discuss the effective and safe use of lasers, light sources, and radiofrequency devices in the clinical management of Asian patients with selected dermatoses.

Acne Vulgaris↗

FK506: therapeutic effects on lupus dermatoses in autoimmune-prone MRL/Mp-lpr/lpr mice.

The effects of FK506, a new immunosuppressive agent, on the development of lupus dermatoses were investigated in the autoimmune-prone MRL/Mp-lpr/lpr (MRL/lpr) mouse, which is an animal model for the spontaneous development of skin lesions similar to those of human lupus erythematosus (LE). FK506 reduced the incidence of skin lesions, lupus nephritis, the titre of serum anti-double-stranded DNA antibodies and the massive T cell proliferation. The incidence and magnitude of IgG deposition at the dermoepidermal junction were not changed. These results suggest that FK506 is a promising immunosuppressive agent for the control of autoimmune skin diseases.

Animals↗

Complement in pemphigus vulgaris and other bullous dermatoses.

The behavior of the complement and of its components C4 and C3 has been studied in serum and in blister fluid both in patients with pemphigus vulgaris and other bullous dermatoses and in healthy subjects with experimentally induced blisters. The results are suggestive of local activation of the complement, in the blister fluid of patients with pemphigus vulgaris, pemphigus erythematosus and bullous pemphigoid according to the classical enzymatic sequence.

Beta-Globulins↗

[The value of oil baths for adjuvant basic therapy of inflammatory dermatoses with dry, barrier-disrupted skin].

The therapeutic value of oil baths for the treatment of dry skin with disturbed barrier function in atopic eczema, atopic xerosis, dry aged skin, exsiccation eczematid and psoriasis vulgaris is presented with special regard to modern concepts of epidermal barrier function. The use of oil baths with emollients as an integral and indispensable constitutent of maintenance therapy in dry skin conditions, atopic eczema and inflammatory dermatoses is reviewed.

Baths↗

[Photodynamic therapy at the threshold of clinical use in disseminated dermatoses].

Photodynamic therapy (PDT) involving the sequential administration of photosensitizing drugs and light has a successful record in the treatment of superficial tumors. Recent investigations document not only cytotoxicity but also immunomodulatory effects of PDT. Cell type as well as state of activation and differentiation are among the parameters influencing susceptibility to PDT, thus allowing targeting of selected cell (sub-)populations. In addition to lasers, non-coherent light sources are also effective. These features, along with current clinical experience, suggest PDT as an interesting alternative to better established photochemotherapies in the treatment of widespread malignant and benign dermatoses.

Humans↗

Comparison of the distribution and numbers of antigen-presenting cells among T-lymphocyte-mediated dermatoses: CD1a+, factor XIIIa+, and CD68+ cells in eczematous dermatitis, psoriasis, lichen planus and graft-versus-host disease.

Antigen-presenting cells (APCs) participate in the initiation of the inflammatory process in various immune-mediated dermatoses through the activation of antigen-specific T lymphocytes. The skin contains several different subsets of APCs. To investigate the role of these APCs in T-cell immune-mediated inflammation, we examined the distribution and numbers of epidermal and dermal CD1a(+) dendritic cells (DCs), factor XIIIa(+) dermal DCs, and CD68(+) macrophages in five T-cell-mediated inflammatory skin diseases. Immunohistochemistry of CD1a, factor XIIIa, and CD68 was performed using paraffin-embedded tissue obtained from a total of 51 patients with eczematous dermatitis (histologically spongiotic dermatitis), psoriasis, lichen planus, acute graft-versus-host disease (GVHD), and chronic GVHD. The numbers of positive cells for each staining were compared with those in site-matched normal skin control specimens from aged-matched subjects. In spongiotic dermatitis and lichen planus, the numbers of epidermal and dermal CD1a(+) cells and factor XIIIa(+) cells were significantly greater than in normal control skin, while in psoriasis only factor XIIIa(+) cells were significantly increased in number. Acute and chronic GVHD showed a reduced number of dermal CD1a(+) cells. Interestingly, factor XIIIa(+) cells were decreased in acute GVHD while they were increased in chronic GVHD. There was a significant reduction in epidermal CD1a(+) cells in acute GVHD, but not in chronic GVHD. The differences in the numbers of APCs in lesional skin appeared to reflect differences in the pathophysiology of these inflammatory skin diseases.

Adolescent↗

The self-inflicted dermatoses: a critical review.

The self-inflicted dermatoses, namely dermatitis artefacta, neurotic excoriations, and trichotillomania, have been reported to be associated with various degrees of psychopathology in the dermatologic literature, but have received surprisingly little emphasis in the psychiatric literature. This probably reflects, firstly the fact that most of these patients initially deny any psychologic problems and hence may not receive psychiatric interventions, and secondly a lack of adequate collaboration between the psychiatrist and dermatologist. These disorders may be associated with serious sequelae, such as suicide and repeated major surgical procedures. Their treatment is also primarily psychiatric. This article critically reviews the literature and comments upon the salient clinical features and treatments for these disorders, which are relevant for the psychiatrist doing consultation-liaison work. Knowledge of these disorders is important in the evaluation of any psychiatric patient, as these disorders are essentially a cutaneous sign of psychopathology.

Dermatitis↗

A prevalence survey of dermatoses in the Australian neonate.

A group of 420 neonates underwent total cutaneous and oral mucosal examinations during the first week of life. Skin lesions were seen in almost every baby (99.3%). The eight most common dermatoses were desquamation (65.0%), Epstein's pearls (56.0%), sebaceous hyperplasia (48.0%), milia (36%), toxic erythema (34.8%), salmon patch (33.8%), hypertrichosis (29.0%), and Mongolian spot (25.5%). Congenital melanocytic nevi were clinically diagnosed in 9 of 420 babies (2.1%); the majority of the lesions were small, that is, less than 1.5 cm in diameter. These neonates had a dark complexion (all had brown or black hair, and most had an olive skin color) and came from families with no previous history of cutaneous melanoma. In contrast, all 19 babies with a previous family history of melanoma had a fair complexion (blond or light brown hair and alabaster skin color) but no congenital melanocytic nevi. These findings may suggest that small congenital melanocytic nevi are markers for persons with a decreased risk of melanoma, because dark-skinned persons are at a lower risk. On the other hand, small congenital melanocytic nevi may be precursors of melanoma. Only prospective studies will determine the magnitude of this risk and thereby optimize management.

Asian People↗

Dermatoses associated with sterile lytic bone lesions.

In recent years several dermatoses, palmoplantar pustulosis, acne fulminans, and Sweet's syndrome, have been associated with sterile lytic bone lesions. This article discusses the clinical, laboratory, and histologic findings of these disorders and postulates a common mechanism underlying the bone lesions.

Bone Diseases↗

A review of two controlled multicenter trials comparing 0.05% halobetasol propionate ointment to its vehicle in the treatment of chronic eczematous dermatoses.

The efficacy and safety of 0.05% halobetasol propionate ointment were evaluated in patients with chronic atopic or other eczematous dermatoses in two vehicle-controlled, double-blind studies: a paired-comparison study in 124 patients (study A) and a parallel-group study in 100 patients (study B). In study A, patients applied both treatments twice daily for 2 weeks and were evaluated by investigators on days 0, 7, and 14 with 0 to 3 severity scales and by self-assessment with two 5-step end-of-treatment rating scales. In study B, patients applied treatments twice daily for 2 weeks, and investigators made evaluations on days 0, 3, 7, and 14 with 0 to 6 scales and also made a 5-step end-of-treatment physician's global assessment. In study A, both severity scores and patient ratings favored halobetasol propionate significantly on days 7 (p less than or equal to 0.0013) and 14 (p less than 0.0001); in study B, severity scores on days 3 (p less than or equal to 0.045, pruritus, erythema, and overall lesion severity), 7, and 14 (p less than 0.001, all comparisons) also favored halobetasol propionate significantly, and global assessments showed complete resolution or marked improvement for 83% of patients using halobetasol propionate versus 28% of those using vehicle (p less than 0.0001). No instances of systemic effects or skin atrophy were reported in either study. We conclude that 0.05% halobetasol propionate ointment is highly effective and well tolerated in the treatment of the conditions studied, with the rapid action and high degree of clearing associated with superpotent corticosteroid formulations.

Adolescent↗

Life-threatening dermatoses due to metabolic and endocrine disorders.

Cardiovascular heart disease due to atherosclerosis is the commonest cause of mortality and morbidity in the Western world. Atherosclerosis is directly related to disorders of lipid metabolism, diabetes mellitus (DM), and insulin resistance. Disorders of thyroid function and porphyrin metabolism occur less frequently but may cause life-threatening situations if unrecognized. All these disorders are associated with characteristic dermatoses, which should permit early diagnosis and meaningful intervention.

Critical Illness↗

Inflammatory noninfectious dermatoses of HIV.

Since the advent of HIV/AIDS, a variety of inflammatory noninfectious skin conditions have been described in HIV-infected patients. This review will discuss a group of inflammatory, noninfectious dermatoses that, although not exclusive to HIV/AIDS, are commonly observed in HIV-infected patients and pose an apparent paradox in a disease that supposedly involves suppression of cellular immunity.

Diagnosis, Differential↗

Development of dapsone toxicity in patients with inflammatory dermatoses: activity of acetylation and hydroxylation of dapsone as risk factors.

BACKGROUND: Alternative independent routes of dapsone metabolism include N-hydroxylation to the hydroxylamine, a potentially toxic metabolite, by cytochrome P450 enzymes and acetylation to a nontoxic metabolite by N-acetyltransferase. Potentially, therefore, the relative extents of these two routes in an individual could determine the occurrence of adverse reaction with dapsone therapy. METHODS: Phenotypic activity of these two routes of metabolism was assessed in 18 patients receiving longterm dapsone therapy for inflammatory dermatoses and was related to the development of dapsone toxicity. N-Hydroxylation was assessed by the dapsone recovery ratio, a ratio of dapsone hydroxylamine to the sum of hydroxylamine and dapsone in 8-hour urine, whereas N-acetylation was assessed by the acetylation ratio, a ratio of monoacetyldapsone to dapsone in 8-hour plasma sample after an oral dose of dapsone. RESULTS: There was wide intersubject variation in both the acetylation ratio and the dapsone recovery ratio, but both phenotypic measures remained stable within individuals. The dapsone recovery ratio showed a tendency toward being lower in fast than in slow acetylators, but this was not statistically significant. There was an inverse relationship between acetylation and hydroxylation (r = -0.69; P < .005) at steady state that was not apparent after the first dose. Neurotoxicity developed in two subjects and hemolytic anemia developed in two subjects. Plasma levels of dapsone in these four subjects were similar to those in subjects who showed no toxicity. All four were slow acetylators and three were rapid hydroxylators, consistent with the toxic nature of dapsone hydroxylamine. CONCLUSIONS: These observations are consistent with what is known about the toxicity profile of dapsone metabolites and suggest that assessing N-acetylation and N-hydroxylation capacities can help to identify subjects at increased risk of a toxic response. This approach of assessing the phenotypic measures of drug-metabolizing activity to predict adverse reaction may also apply to other drugs with metabolic-based adverse effects.

Acetylation↗

Neutrophilic dermatoses and myeloproliferative disease: report of two cases.

The term "neutrophilic dermatosis" has been suggested for a spectrum of skin lesions that have been noted in some patients with myeloproliferative diseases. These cutaneous conditions vary from plaques typical of Sweet's syndrome to bullous and pyodermatous lesions. We describe two patients with neutrophilic dermatoses and myeloproliferative disorders. Distinctive features included concurrent bullous pyodermatous lesions and characteristic lesions of Sweet's syndrome in one patient and overwhelming sterile pulmonary infiltration in the other patient. These disorders may be difficult to distinguish from acute infectious processes, and they may have systemic components, including pneumonitis. Possible therapeutic alternatives to systemic corticosteroid therapy are suggested.

Aged↗

Allergic dermatoses.

Defining "allergy" and elucidating the immunopathology of what is too often described as allergic rashes is the objective of this article. The differentiation of inflammatory reactions, which at times is indistinguishable from the immunologic dermatoses is outlined. A rationale plan for management, with indications warranting referral to "the specialist" are suggested.

Autoimmune Diseases↗

Neutrophilic vascular dermatoses.

The neutrophilic vascular dermatoses are a divergent group of disorders with distinct cutaneous manifestations. Diagnosis of these diseases requires clinical acumen because of the lack of pathognomonic histopathologic features. It is important for physicians to recognize these entities because of the large number of possible associated underlying diseases.

Humans↗