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Objective: STI571 is a tyrosine kinase inhibitor which inhibits the kinase activity of kit, the receptor for stem cell factor (SCF). Because activating mutations of c-kit affecting codon 816 are associated with human mast cell neoplasms, we determined whether STI571 exerted a similar cytotoxic effect on neoplastic and normal human mast cells., Methods: We investigated the effect of addition of STI571 in increasing concentrations (0.01 to 10 micromolar) to two HMC-1 human mast cell leukemia cell lines carrying two different activating c-kit mutations in codons 816 or 560, as well as the effect of the drug on short-term bone marrow cultures obtained from patients who carry a mutated codon 816 or wild-type c-kit., Results: STI571 failed to inhibit the growth of HMC-1(560,816) cells bearing a codon 816 mutation but effectively suppressed the proliferation of HMC-1(560) carrying c-kit with the wild-type codon 816. STI571 did not induce preferential killing of neoplastic bone marrow mast cells in short-term cultures from patients bearing a codon 816 c-kit mutation. In contrast, STI571 caused a dramatic reduction in mast cells in patients without codon 816 c-kit mutations., Conclusion: These results suggest that STI571, while effectively killing mast cells with wild-type c-kit, did not show preferential cytotoxicity to neoplastic human mast cells and thus may not be effective in the treatment of human systemic mastocytosis associated with codon 816 c-kit mutations.

Background: Cutaneous involvement occurs in most patients with systemic mastocytosis., Objective: We sought to determine whether the extent of cutaneous involvement is predictive of systemic disease., Methods: In a prospective survey of 48 adults and 19 children, the extent and density of cutaneous lesions were compared with patient history, symptoms, internal organ involvement, serum total mast cell tryptase level, and bone marrow pathology., Results: Cutaneous lesions in children were of a greater mean and maximum diameter, but similar in extent and density compared with lesions in adults. In adults with skin lesions, the extent of lesions correlated to disease duration. Adults with extensive cutaneous disease experienced more pruritus and flushing. Fatigue, splenomegaly, and hepatomegaly were more frequent in adults without cutaneous involvement; and in those with a greater density of lesions and disease duration. Increased tryptase levels were found in children and adults with systemic disease and correlated to skin lesion density and bone marrow pathology., Conclusion: An examination of the extent and density of cutaneous lesions in adults helps identify those with more extensive extracutaneous disease and, thus, requiring a more thorough evaluation.

Oranges are suspected of inducing adverse skin reactions in patients with atopic eczema. We studied 21 adult patients with atopic eczema and a history of adverse reactions to oranges and 10 patients without. A dietary history, skin tests, serum IgE and oral provocation tests with oranges were obtained. Severity of eczema was monitored by SCORAD, and serum tryptase, eosinophil cationic protein and urinary methylhistamine were measured. No allergic reactions were found to orange in skin prick or patch tests. However, 23 patients (74%) had specific serum IgE to orange. Oral provocation testing resulted in pruritic eczematous or maculopapular skin lesions predominantly at the predilection sites in 16 patients (52%). The SCORAD increased significantly in patients positive to the oral provocation test (p <0.05). Specific IgE to orange did not correlate with the clinical outcome of the oral provocation test. No significant changes were found in serum mast cell tryptase, eosinophil cationic protein or in urinary methylhistamine excretion. The negative results in the skin tests and a lack of correlation between specific IgE and oral provocation tests indicate that non-IgE-mediated mechanisms are involved in cutaneous adverse reactions to oranges in patients with atopic eczema.

Objective: To determine clinical correlates of urticaria pigmentosa (UP) regression in adult patients with systemic mastocytosis (SM)., Design: Cohort study of the natural history of mastocytosis., Setting: National Institutes of Health Clinical Center., Patients: In a study of adult patients referred to the National Institutes of Health after 1980 and observed for a minimum of 10 years, 12 of 106 adult patients experienced clearance or fading of UP., Main Outcome Measures: Data from each patient's history and results of physical examination, laboratory evaluation, and organ biopsy at presentation to the National Institutes of Health were compared with findings at the patient's most recent visit., Results: In the patients in whom clearance of (n = 5) or a decrease in skin lesions (n = 7) was noted, UP had persisted from 4 to 34 years (median, 17 years). Older age was a prognostic feature for regression of UP. Despite improvement of UP, the 2 patients with SM with an associated hematologic disorder experienced a deterioration in clinical condition. In the 10 patients with indolent SM, severity and frequency of symptoms decreased as the UP regressed. However, bone marrow changes consistent with SM remained., Conclusions: Urticaria pigmentosa regresses in approximately 10% of the older patients who have SM. In patients with an associated hematologic disorder such as myelodysplasia, this regression may be accompanied by disease progression. In contrast, regression of UP in patients with indolent SM parallels a decrease in disease intensity, although bone marrow findings of indolent SM remain.

Adverse drug reactions (ADR) are an important clinical problem. They account for about 5% of all hospital admissions and cause death in approximately 0.01% of surgical patients. The mechanisms leading to ADR beyond IgE-mediated allergy are still poorly understood. The importance of chemically reactive drug metabolites and the involvement of T-lymphocytes in many drug hypersensitivity reactions have been highlighted in recent years. ADR are diagnosed on clinical grounds and the temporal relation between drug intake and the appearance of the symptoms. Allergy tests are required in the further assessment of the reaction. By means of skin tests, in vitro tests and provocation tests information about the culprit drug, the mechanism involved and possible alternatives can be obtained., (Copyright 2002 S. Karger AG, Basel)

Background: Mast-cell accumulation has been observed in the skin and other organs of patients with systemic indolent mastocytosis (SM). The basis for this pathologic increase is not fully understood., Objective: We sought to determine levels of mast-cell growth factors in the skin and plasma of patients with SM, patients with atopic dermatitis (AD), and healthy individuals and to correlate these levels to dermal mast-cell numbers and levels of mast-cell tryptase., Methods: Skin suction blister fluid and plasma levels of stem-cell factor, IL-3, IL-4, IL-6, vascular endothelial growth factor, and total mast-cell tryptase were analyzed by means of ELISA. The number of mast cells was determined in a biopsy section taken from adjacent skin., Results: Mast-cell numbers in the dermis were higher in patients with SM compared with numbers in patients with AD (P <.001) or in healthy control subjects (P <.0001) and correlated with tryptase levels in both skin blister fluid (P <.0001) and plasma (P <.0001). Stem-cell factor and vascular endothelial growth factor levels in the skin blister fluid and plasma of patients with SM were not significantly different from those in patients with AD or healthy control subjects. IL-3 and IL-4 levels were below the limit of detection. IL-6 levels were significantly increased in the plasma of patients with SM compared with in plasma of patients with AD (P <.002) and healthy control subjects (P <.0001) and correlated with plasma tryptase levels (P <.05) and dermal mast-cell numbers (P <.02)., Conclusion: Because elevated levels of IL-6 could contribute to the fever, fatigue, and osteoporosis observed in patients with SM and because IL-6 is antiapoptotic for mast cells, IL-6 could potentiate the biologic consequences of this disease.

Mastocytosis is defined by a pathological increase in mast cell numbers in tissues. Recent clinical observations on rare manifestations highlight the diversity of this disease. The diagnosis is now aided by new surrogate markers. At the molecular level, recent studies have reinforced the role of activating mutations in KIT in the etiology of mastocytosis. These findings provide a conceptual basis for the development for new therapeutic strategies.

A 92-year-old immobilized white woman under the daily nursing care of a private ambulatory nursing service displayed acquired deformities of the toenails resembling a ram's horn. In light of a rapidly growing elderly population, this case report illustrates the need for close monitoring of the quality of care that nursing services provide to older persons. In addition, it reviews the clinical aspects of onychogryphosis, as well as its pathomechanisms and treatment options.

Allergic reactions to foods represent a prominent, actual and increasing problem in clinical medicine. Symptoms of food allergy comprise skin reactions (urticaria, angioedema, eczema) respiratory (bronchoconstriction, rhinitis), gastrointestinal (cramping, diarrhea) and cardiovascular symptoms with the maximal manifestation of anaphylactic shock. They can be elicited by minute amounts of allergens. The diagnosis of food allergy is done by history, skin test, in vitro allergy diagnosis and--if necessary--oral provocation tests, if possible placebo-controlled. Avoidance of respective allergens for the allergic patient, however, is often complicated or impossible due to deficits in declaration regulations in many countries. Increasing numbers of cases including fatalities, due to inadvertent intake of food allergens are reported. It is therefore necessary to improve declaration laws and develop methods for allergen detection in foods. Allergens can be detected by serological methods (enzyme immunoassays, in vitro basophil histamine release or in vivo skin test procedures in sensitized individuals). The problem of diagnosis of food allergy is further complicated by cross-reactivity between allergens in foods and aeroallergens (pollen, animal epithelia, latex etc.). Elicitors of pseudo-allergic reactions with similar clinical symptomatology comprise low-molecular-mass chemicals (preservatives, colorings, flavor substances etc.). For some of them (e.g. sulfites) detection assays are available. In some patients classic allergic contact eczema can be elicited systemically after oral intake of low-molecular-mass contact allergens such as nickel sulfate or flavorings such as vanillin in foods. The role of xenobiotic components in foods (e.g. pesticides) is not known at the moment. In order to improve the situation of the food allergic patient, research programs to elucidate the pathophysiology and improve allergen detection strategies have to be implemented together with reinforced declaration regulations on a quantitative basis.

Background: Most treatment protocols for vitiligo require a long treatment duration and usually do not result in complete repigmentation. Therefore, cosmetically acceptable and easily to handle alternatives are warranted., Objective: To evaluate the properties of dihydroxyacetone (DHA) in a new formulation for the treatment of vitiligo on exposed areas., Methods: We treated 10 patients suffering from vitiligo affecting the face and/or hands with a newly introduced, commercially available self-bronzing cream containing DHA 5%. DHA was applied every second day., Results: The characteristic pigmentation showed very satisfactory cosmetic results in 8 out of 10 patients after 2 weeks of treatment., Conclusion: The new DHA formulation is a practical and well-accepted treatment modality., (Copyright 2001 S. Karger AG, Basel)

Background: Tinea capitis is the most common dermatophytosis of childhood with increasing incidence. Whereas griseofulvin is considered by many as the mainstay of treatment, newer oral antifungal agents, including fluconazole, itraconazole and terbinafine have demonstrated higher efficacy, resulting in shorter treatment durations., Objectives: We aimed to determine the optimum regimen for the treatment of childhood tinea capitis with itraconazole., Methods: A mycological culture outcome-dependent combination of a 28-day continuous and facultative additional 14-day courses with itraconazole was used in 42 children (20 girls; 22 boys) aged 12-140 months (mean 66) with tinea capitis due to Microsporum canis (n = 26) and Trichophyton violaceum (n = 16). The drug was given orally according to the patients' body weight (50 mg daily for < 20 kg; 100 mg daily for > or = 20 kg) over 4 weeks. Direct microscopy and fungal culture as a parameter for efficacy were repeated 2 weeks after termination of treatment. Assessment of efficacy was based on the evaluation of results from light microscopy and culture at 8 weeks after initiation of treatment, and in the case of a further positive mycological culture at 14 and 20 weeks, respectively. A positive fungal culture at these times resulted in an additional course for 2 weeks with the initially chosen itraconazole dosage., Results: In 34 of 42 patients a single 4-week course of itraconazole resulted in a complete mycological cure of lesions as demonstrated by light microscopy and mycological culture. Four of 42 patients had to be treated by a second itraconazole course for 2 weeks, and four children received a third course of itraconazole for 2 weeks until all lesions showed negative direct microscopy and mycological culture. No abnormal haematological or biochemical results occurred. Apart from transient, completely reversible indigestion in two children, no side-effects were observed., Conclusions: A culture-based 28-day continuous therapeutic regimen plus facultative cultural outcome-dependent additional 14-day courses of a body weight-adapted dosage of itraconazole in tinea capitis due to M. canis and T. violaceum is discussed; this offers the advantage of an effective therapy with complete negative direct microscopy as well as negative cultural results, within a shorter active treatment period (cf. previous studies with continuous administration of itraconazole).

Fourteen patients suffering from acute, exacerbated atopic eczema were screened for changes in collagen I and collagen III metabolism in serum (n = 11), urine (n = 11) and skin biopsies (n = 9) before and after medium-dose ultraviolet (UV) A1 phototherapy (15 exposures of 50 J/cm2 over a 3-week period, total dose 750 J/cm2). Mature collagen I and, to a lesser extent, mature collagen III were found to be decreased after the therapy in skin samples from the irradiated patients. As markers of collagen I degradation, the cross-links pyridoline and deoxypyridoline were analysed in urine using high-performance liquid chromatography. Both cross-links were found to be mildly increased after UVA1 phototherapy, without reaching statistical significance. As markers of de novo collagen synthesis we screened for the procollagen I-carboxyterminal peptide (PICP) and procollagen III-aminoterminal peptide (PIIINP) levels in serum and skin. The ratio of PICP to PIIINP in serum dropped significantly after the UVA1 phototherapy, suggesting a different impact of UVA1 on the two collagens. These findings were paralleled by a diminished ratio of PICP to PIIINP in tissue samples. Staining for matrix metalloproteinase 1 (MMP-1) and its specific counterpart, tissue inhibitor of MMP-1 (TIMP-1), showed slight increases for both proteins by therapeutic UVA1; this was also seen in serum for TIMP-1 but not MMP-1. In our study, high-energy UVA1 doses induced changes of the skin collagens in patients with atopic eczema which are measurable by their metabolites in serum and urine.

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.

Urticaria is one of the most common and, in its chronic course, excruciating dermato-allergic diseases. Apart from the dermatological diagnosis, the identification and evaluation of causal triggering factors is of utmost importance. Here a 'three-step guideline' (according to Ring and Przybilla) has gained acceptance, ranging a general basic examination via an intensive investigation until oral provocation tests for food allergy and oral provocation tests for idiosyncrasy (OPTI) against food additives. Apart from true IgE-mediated allergies, pseudo-allergic reactions against food additives as well as food contents represent a major problem in chronic urticaria. Recently gastric mucosal colonization with Helicobacter pylori as the trigger of chronic urticaria has received attention. New pathophysiological concepts describe autoantibodies that are directed either against IgE or against the high-affinity IgE-receptor on the surface of mast cells and basophil leucocytes. In the intradermal test with autologous serum positive wheal and flare reactions can be observed (Greaves' test). In many patients with chronic urticaria considerable psychosomatic involvement is also observed. Histamine is one of the major mediators of most forms of urticaria although in some cases, especially physical urticaria, other mediators seem to play a role. Therefore antihistamines, and mainly H1 antihistamines, are the mainstay of antiurticaria therapy. Some studies have shown a benefit of combined H1- and H2-antagonist treatment in special forms of urticaria namely urticaria factitia. Similarly pretreatment with combined H1 and H2 antagonists has been proven to reduce effectively the frequency of pseudo-allergic reaction to some histamine-releasing drugs used in radiology or surgery. More than 50 years after the first introduction of an antihistamine into allergy therapy, antihistamines still represent modern and exciting agents contributing to the continuous improvement of antiallergic therapy. Antihistamine therapy can be performed with either the classical or second generation antihistamines. Classical antihistamines are connected with considerable side-effects especially sedation and anticholinergic effects. New non-sedating antihistamines have been developed that do not cross the blood-brain barrier. The efficacy of mizolastine, a new non-sedating H1 antagonist, has been evaluated in several placebo-controlled and comparative clinical trials. Overall, mizolastine 10 mg/day was found to be significantly more effective than placebo and as effective as other second generation antihistamine drugs in the management of patients with chronic urticaria, with a rapid and sustained action.

In the last few years delayed reactions several hours after the injection of radiographic and contrast materials (PRC) have been described with increasing frequency. The authors report two observations on patients with delayed reactions in whom intradermoreactions (IDR) and patch tests to a series of ionic and non ionic PRC were studied. After angiography by the venous route in patient n degree 1 a biphasic reaction with an immediate reaction (dyspnea, loss of consciousness) and delayed macro-papular rash appeared, whilst patient n degree 2 developed a generalised sensation of heat, persistent pain at the site of injection immediately and a generalised macro-papular reaction after 24 hours. The skin tests revealed positive delayed reactions of 24 hours and 48 hours by IDR and patch tests to only some PRC with common chains in their structures. The positive skin tests are in favour of immunological reactions and may help in diagnosis of allergy in the patients.

Background: In atopic eczema (AE), skin colonization with Staphylococcus aureus plays a possible role in the pathophysiology of the disease., Methods: Thirty-eight patients with AE were screened for their cutaneous colonization with S. aureus. The antibacterial and clinical efficacy of topical therapy with the antiseptic dye gentian violet, a potent glucocorticosteroid or a tar solution (liquor carbonis detergens) was evaluated in vivo in 21 patients with a density of >10(4) CFU/cm(2) and in vitro. Skin sites were treated twice daily for 4 days with the active drug or a corresponding control. Quantification of S. aureus was done daily during therapy as well as 3 days thereafter. The severity of the lesions was rated by a regional SCORAD., Results: In gentian-violet-treated skin, bacterial density decreased significantly in lesional (p < 0.001) and unaffected skin (p < 0. 001). Bacterial densities did not decrease during therapy with glucocorticosteroid or liquor carbonis detergens but dropped afterwards. All therapeutics reduced the severity score, reduction being greatest for the glucocorticosteroid and lowest for liquor carbonis detergens. In vitro, a high antibactericidal efficacy was demonstrated only for gentian violet., Conclusions: Antibacterial therapy with gentian violet not only reduces S. aureus dramatically, but also reduces the severity of the eczema. Reduction of S. aureus after therapy with glucocorticosteroids and LCD seems to be secondary to improvement of the skin condition.

Background: Some clinical studies suggest that a combination of an H1- and H2-antagonist may be effective in the prophylaxis of allergic reactions., Objective: The efficacy of pretreatment with an H1/H2-antagonist combination, H1-antagonist alone, or placebo in the prophylaxis of local and systemic adverse reactions to specific immunotherapy with Hymenoptera venom was compared., Methods: In a prospective, randomized, double-blind, placebo-controlled study, 121 patients with Hymenoptera venom allergy were treated with rush immunotherapy and pretreatment with one of the following: 120 mg of terfenadine plus 300 mg of ranitidine, 120 mg of terfenadine alone, or placebo. The incidence of unwanted systemic adverse and local reactions was recorded for up to 50 weeks., Results: In seven patients (6%), six in the placebo group and one in the terfenadine group, systemic side effects required cessation of therapy (p = 0.005). Subjective symptoms occurred in four patients (10%) in the terfenadine plus ranitidine group and in three patients (7%) in the terfenadine group. Regarding local reactions, significantly fewer patients treated with a combination of terfenadine and ranitidine and with terfenadine alone as compared with placebo had severe local symptoms of erythema (29%, 29%, and 49%), edema (24%, 18%, and 41%), and pruritus (13%, 11%, and 31%) at week 1 (p < 0.05). This therapeutic benefit was limited to the first 4 weeks of treatment. Treatment with a combination of terfenadine and ranitidine was not superior to treatment with terfenadine alone., Conclusions: Pretreatment with H1-antihistamines with or without H2-antihistamines significantly reduced local and systemic adverse reactions to immunotherapy with Hymenoptera venom and may therefore be helpful in the management of immunotherapy.

A 12-year-old girl developed acanthosis nigricans due to increased levels of serum insulin. Hyperinsulinemia has been recognized as the underlying cause in most cases of acanthosis nigricans. In this paper we outline a typical clinical case with special regard to the proposed pathogenesis.