Immunophenotyping of inflammatory cells in lesional skin of the extrinsic and intrinsic types of atopic dermatitis.

BACKGROUND: There is a subgroup of atopic dermatitis (AD) patients with normal total and specific IgE levels and negative skin tests towards common allergens. This form of the disease has been referred to as the 'intrinsic' form of AD. Although previous studies have demonstrated differences in the cytokine profile between the extrinsic and intrinsic subtypes, the pathogenesis of both subtypes of AD remains unclear. OBJECTIVES: To compare the inflammatory micromilieu in both forms of AD. METHODS: Immunophenotyping of the inflammatory cells was performed in lesional and nonlesional skin from 18 patients with extrinsic and 17 with intrinsic AD. RESULTS: Immunohistochemical analysis revealed a high proportion of CD4+ T cells in the dermis, with a similar CD4/CD8 ratio in the two groups. The expression levels of other T-cell markers and epidermal Langerhans cells were increased in both forms of AD. Although the T-cell repertoires in the two subtypes were similar, dermal infiltration of eosinophils and eosinophil granular proteins was more prominent in the extrinsic type than in the intrinsic type. Eotaxin immunoreactivity was also significantly higher in the extrinsic subtype. CONCLUSIONS: The data suggest that although the overall inflammatory microenvironment in the two subtypes appears to be similar, differences in T-cell cytokine production might contribute to the differential tissue eosinophilia in these subtypes.

Histopathological parameters determining lesion colours in the naevus of Ota: a morphometric study using computer-assisted image analysis.

BACKGROUND: Naevus of Ota manifests various colours ranging from light brown to blue. Naevus colours have been claimed to reflect the depth of melanin pigments but the claim has rarely been substantiated by quantitative studies. OBJECTIVES: We attempted both quantitative and qualitative analyses of the naevus of Ota to find out relations between histological patterns or parameters of melanin/melanocytes and lesion colours. METHODS: Lesion colours were determined by one of the authors and were confirmed by a separate panel of dermatologists. Forty biopsy specimens of naevus of Ota were evaluated by both computer-assisted quantitative image analysis and a previously proposed conventional pattern analysis. RESULTS: The mean area fraction (AFmean) of melanin, the depth of the maximum area fraction of melanin (level of AFmax) and the depth of the deepest infiltrating melanocyte were significantly greater or deeper for bluish lesions than brownish lesions. Based on the qualitative pattern analysis we found that all the brownish lesions demonstrated superficial dermal melanin pigments, whereas bluish lesions tended to show more heterogeneous histological patterns. Eyelid lesions, all of which were bluish, revealed greater AF(mean) value than cheek lesions, presenting as either brownish or bluish colours. CONCLUSIONS: Quantitative analysis indicated that pigment density measures such as AFmean could be as important as the depth of melanocytes in the explanation of the lesion colours in naevus of Ota. However, qualitative pattern analysis failed to link specific patterns with lesion colours, especially in bluish lesions, probably due to the lack of consideration of the pigment density.

Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR.

BACKGROUND: A small subgroup of atopic dermatitis (AD) patients with normal serum IgE levels and without specific IgE sensitization has been termed 'intrinsic type of AD' (ADi) as a counterpart to the term 'extrinsic type of AD' (ADe). However, there are neither molecular markers nor clinically diagnostic tools for distinguishing between ADi and ADe. OBJECTIVE: The present studies were undertaken to clarify the pathogenesis and in vivo cytokine micromilieu of ADi patients in comparison with ADe patients. METHODS: We used semiquantitative RT-PCR to investigate the expression of various cytokines and assessed the tissue eosinophil counts in skin biopsies from both types of AD patients. RESULTS: Although there was no significant difference of cellular infiltrates in the lesional skin between ADe and ADi patients, ADe had significantly increased tissue eosinophilia than ADi. Based on our RT-PCR, the expression patterns of cytokines could be categorized into four groups. The first group includes IL-5, IL-13, and IL-1beta, whose levels of mRNA expression were higher in both types of AD patients than non-atopic (NA) subjects, while ADe patients had even higher levels than ADi patients. The second group includes interferon-gamma (IFN-gamma), IL-12, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-4, and IL-10, whose levels of mRNA expression were elevated in both types of AD patients without differences between ADe and ADi patients. The third group includes tumour necrosis factor-alpha (TNF-alpha), whose mRNA expression was more decreased in both types of AD patients than NA, and the fourth group includes IL-6 and transforming growth factor-beta (TGF-beta), which did not show any differences among the three groups. CONCLUSION: These current data demonstrate that the expressions of cytokines IL-5, IL-13, and IL-1beta mRNA and the number of dermal infiltrating eosinophils are increased in ADe patients compared with ADi patients.

Calcified nodule on the heel of a child following a single heel stick in the neonatal period.

Dystrophic cutaneous calcification may arise at sites of local trauma or in association with various disorders. Calcified nodules of the heel have been reported in high-risk neonates following repeated heel sticks to draw blood. We present a healthy 2-year-old boy with a calcified nodule on the heel secondary to a single heel stick in the neonatal period. The patient was born full-term at 38 weeks' gestation, with a birth weight appropriate for gestational age. A firm nodule was noticed at the age of 8 months; this became tender. Histology revealed epidermal and subepidermal deposition of calcium. Serum calcium and phosphate levels were normal. Although calcified heel nodules occur mostly in high-risk neonates, this case suggests that this condition also can occur in healthy children after only a single heel stick. Dermatologists should include this entity in the differential diagnosis of warty papules on the heels of children.