Hugo Degreef

Identification of cross‐reaction patterns in allergic contact dermatitis from topical corticosteroids

Contact allergy to topical corticosteroids occurs more frequently than previously supposed. Cross‐allergic phenomena are common. On the basis of a review of the literature and our own patch test data on 15 patients, we conclude that positive patchtests to corticosteroids occur approximately six to seven times more frequently in well‐defined groups of structurally‐related substances than between corticosteroids of different groups. An analogous substitution pattern on the steroid D‐ring or the carbon side chain (C20, C21) seems to have a significant influence on the association of positive patchtest results. This is not the case for other structural variables, such as the presence of a double bond in the steroid A‐ring or fluoride substitutions on the B‐ring. The effect of other factors such as concomitant sensitization and steroid metabolism in the skin on the development of a corticosteroid polyallergy are analysed, and the specificity and sensitivity of cross‐allergy phenomena are evaluated. These are important in the selection of a topical steroid in the future treatment of a corticosteroid sensitive patient.

Pharmacokinetic profile of orally administered itraconazole in human skin

Itraconazole is an orally effective antifungal agent with a high affinity for tissues. The skin kinetics in human volunteers have been studied after administration of 100 and 200 mg of itraconazole daily. From day 7 onward, tissue levels in the beard region and on the back were consistently higher than the corresponding plasma levels. The levels in the palmar stratum corneum were lower than the corresponding plasma levels but persisted for 3 weeks after discontinuation of therapy. Stratum corneum levels in the beard area were still measurable 4 weeks after the end of therapy. With the 200-mg dose, sweat levels became detectable 24 hours after the first drug intake. The sweat levels were usually lower than the corresponding plasma levels and followed the same curve as the plasma levels. Sebum levels of itraconazole were 10 times as high as the corresponding peak plasma levels. Sebum levels were undetectable 14 days after discontinuation of therapy. The results indicate that oral intake of itraconazole will result in therapeutic levels in the skin and these levels vary, depending on the region of skin tested. There are at least three routes of delivery of itraconazole to the skin: (1) passive uptake by keratinocytes in the basal layer (as shown by the continued presence of the drug in the palmar stratum corneum at a moment when plasma, sebum, and sweat levels are again undetectable); (2) a less significant excretion through the sweat glands (as shown by the lower drug levels compared with the plasma levels); and (3) a massive excretion through the sebaceous glands (as shown by the sebum levels compared with the plasma levels).

ATOPIC DERMATITIS : TRIGGERING FACTORS

Atopic dermatitis is a hereditary disorder, frequently associated with allergic rhinitis and bronchial asthma. The disease may be influenced by many triggering factors such as irritants, aeroallergens, food, microbial organisms, sex hormones, stress factors, sweating, and climatologic factors. Moreover, it is important to be aware of contact allergy as a complicating factor. This review deals with recent clinical, experimental, and some therapeutic data on these triggering factors.

Protein contact dermatitis: myth or reality?

Protein contact dermatitis is a dermatosis which usually presents as a chronic eczema with episodic acute exacerbations a few minutes after contact with the offending allergen. Patch tests with the responsible allergen are usually negative, and the diagnosis can only be made by means of scratch or prick tests with the allergen. Sometimes, specific IgE antibodies can be detected in the blood. As there is considerable confusion about this entity, we have reviewed the cases reported in the literature.

1,25‐dihydroxyvitamin D3 inhibits ultraviolet B‐induced apoptosis, Jun kinase activation, and interleukin‐6 production in primary human keratinocytes

We investigated the capacity of 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] to protect human keratinocytes against the hazardous effects of ultraviolet B (UVB)‐irradiation, recognized as the most important etiological factor in the development of skin cancer. Cytoprotective effects of 1,25(OH)2D3 on UVB‐irradiated keratinocytes were seen morphologically and quantified using a colorimetric survival assay. Moreover, 1,25(OH)2D3 suppressed UVB‐induced apoptotic cell death. An ELISA, detecting DNA‐fragmentation, demonstrated that pretreatment of keratinocytes with 1,25(OH)2D3 1 μM for 24 h reduced UVB‐stimulated apoptosis by 55–70%. This suppression required pharmacological concentrations 1,25(OH)2D3 and a preincubation period of several hours. In addition, 1,25(OH)2D3 also inhibited mitochondrial cytochrome c release (90%), a hallmark event of UVB‐induced apoptosis. Furthermore, we demonstrated that 1,25(OH)2D3 reduced two important mediators of the UV‐response, namely, c‐Jun‐NH2‐terminal kinase (JNK) activation and interleukin‐6 (IL‐6) production. As shown by Western blotting, pretreatment of keratinocytes with 1,25(OH)2D3 1 μM diminished UVB‐stimulated JNK activation with more than 30%. 1,25(OH)2D3 treatment (1 μM) reduced UVB‐induced IL‐6 mRNA expression and secretion with 75–90%. Taken together, these findings suggest the existence of a photoprotective effect of active vitamin D3 and create new perspectives for the pharmacological use of active vitamin D compounds in the prevention of UVB‐induced skin damage and carcinogenesis. J. Cell. Biochem. 89: 663–673, 2003.

Contact dermatitis caused by airborne agents: A review and case reports

A general review is given of airborne-induced contact dermatoses, particularly of the irritant and allergenic types. Because the reports in the literature often omit the term airborne, 12 volumes of Contact Dermatitis (January 1975-July 1985) were screened, and the cases cited were classified in function of the anamnesis, lesion locations, causative irritants and allergens, and other factors. The present article also discusses differential diagnoses, in particular with regard to contact dermatitis of the face, ears, and neck. Finally, seven case reports of occupational and nonoccupational contact dermatitis problems caused by airborne agents are presented. In some of the cases the allergens have not been mentioned in published literature previously.

Clinical forms of dermatophytosis (ringworm infection).

Dermatophytic infections of the skin, hairs and nails are very common and are very variable in aspect. In skin, inflammatory symptoms are often absent, but in other cases they may be very pronounced, in particular when caused by zoophilic dermatophytes. In onychomycosis, it is very difficult to make the differential diagnosis with other causes of onychodystrophy on purely clinical grounds; indeed, even in case of fungal infection, the causative agent can be suspected on clinical grounds only in a minority of cases. The clinical presentation of skin infections, infections of the scalp and beard, and the nails are presented more in detail.

Expression of the endothelin-B receptor in pigment cell lesions of the skin

Abstract. Endothelins (ETs) exert several functions in human melanocytes, including proliferation, dendrite formation, and melanin synthesis. Among the ET receptors, the non-selective endothelin-B (ETB) receptor is the major receptor in melanocytes and malignant melanoma (MM) cells. In spite of the important role of ETs and their receptors in the growth and differentiation of melanocytes, the distribution and expression levels of ETB receptors in tissue sections of benign and malignant pigment cell lesions is still unknown. We combined immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to study ETB receptor expression in benign and malignant pigment cell lesions and in normal skin. Immunohistochemistry on paraffin-embedded tissue sections of 159 cases revealed a significant increase in intensity of ETB receptor expression from common nevi over dysplastic nevi and primary MM to metastatic MM. Quantitative PCR using real-time detection on 75 samples confirmed the immunohistochemical results. These data add the ETB receptor to the growing list of tumor progression markers in MM and suggest that ETs play a role in the progression of MM in the skin.

Contact allergy to corticosteroids: A frequently missed diagnosis?

Contact allergy to corticosteroids is more prevalent than previously recognized and often goes undetected. Nineteen patients with corticosteroid contact allergy are presented. Sixteen reacted to tixocortol pivalate and also to other corticosteroids, particularly to hydrocortisone, which could explain exacerbations of eczema in these cases. Tixocortol pivalate may be a useful marker for screening patients for contact sensitivity to several corticosteroids.

Processing Emotional Information in Alzheimer's Disease: Effects on Memory Performance and Neurophysiological Correlates

Background: There is some impairment of the ability of patients with Alzheimer’s disease (AD) to perceive emotions, but this ability seems relatively preserved compared to the impairment of other cognitive domains. Few studies have focused on the link between emotional processing and other cognitive functions, such as memory or attention. Objective: This study was designed to investigate whether the emotional content of a text can influence memory in patients affected by AD and whether this effect is related to attentional processes as measured by event-related potentials (ERP). Methods: All subjects were administered neuropsychological tests and a logical memory test including emotional and nonemotional material. ERP were recorded during an attention task. Results: AD patients had better immediate recall of sad and, to a lesser extent, happy stories than of neutral stories. This difference also affected multiple choice recognition and identification (immediate and delayed) of emotional content. The amplitude of both P300 and mismatch negativity was significantly decreased in the group as a whole. There was no correlation between P300 parameters and performance on the memory tasks, whatever their emotional content. Conclusions: The results show relatively preserved emotional processing in patients with AD and suggest that the emotional content of a context can influence memory performance. We found no evidence that this effect is mediated by attention as measured by ERP.