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Notes: Melanocortin receptors (MC-Rs) mediate the biological actions of the members of melanocortin family, e.g. of α-melanocyte-stimulating hormone (α-MSH) and adrenocorticotropin. We recently reported that human dermal fibroblasts derived from newborn foreskin express MC-1R. In these cells and in a newborn mouse model of cutaneous fibrosis, α-MSH suppressed collagen synthesis induced by the profibrotic cytokine transforming growth factor-β1(Böhm et al., J. Biol. Chem. 2004). Here, we show that MC-1R expression is maintained in various fibroblastic skin cell types established from adult human skin. In vitro, expression of MC-1R at the RNA level was detected by RT-PCR analysis in dermal fibroblasts, dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle, as well as in HT1080 fibrosarcoma cells. In all of the latter cell types except in HT1080 cells, MC-1R immunoreactivity could be visualized on the cell surface as demonstrated by immunofluorescence studies using an antibody against the amino acids 2–18 of the N-terminal domain of human MC-1R. In situ, MC-1R expression was detectable in interfollicular dermal fibroblasts only by immune electron microscopy. In contrast, MC-1R expression was detectable in dermal papilla cells and connective tissue sheath fibroblasts of the hair follicle by conventional immunohistochemistry. To further assess the relevance of MC-1R being expressed in fibroblastic cells of the skin we treated human dermal fibroblasts in vitro with the proinflammatory cytokine interferon-γ(IFN-γ). α-MSH significantly suppressed the upregulating effect of this cytokine on the expression of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule crucially involved in recruitment of activated leukocytes into the hair follicle. In summary, our findings form a basis upon which MC-1R expression can be investigated in inflammatory disorders affecting the connective tissue compartment of the skin. Moreover, our preliminary data on the modulation of IFN-γ-driven upregulation of ICAM-1 by α-MSH suggest additional functions of melancortins in fibroblasts beyond collagen synthesis.

Notes: Severe generalized nodular and bullous mastocytosis of the xanthelasmoid type is described in a 7-month-old boy. Reddish to yellowish-brown xanthelasmoid papules and nodules first developed in the inguinal region a few weeks after birth and then progressively spread to cover nearly the entire body surface. There was severe pruritus and recurrent episodes of blistering. The diagnosis of cutaneous mastocytosis of the xanthelasmoid type with subepidermal bullae was confirmed by skin biopsies showing solid and deeply penetrating infiltrates of metachromatic mast cells under light and electron microscopy. Systemic involvement of other organs, however, was excluded by bone scintigraphy, abdominal ultrasound, bone marrow aspiration and echocardiography. The extensive skin involvement was reflected in highly elevated urinary levels of histamine (263·4 μg L−1) and its metabolite N-methylimidazole acetic acid (20·8 mg L−1). The patient was systematically well and received only symptomatic treatment. Over a period of 1 year, the condition gradually improved, and the skin lesions began to flatten and regress.

Notes: Summary Metastatic calcinosis is a common feature of chronic renal failure. Its first manifestations are bone demineralization and non-visceral and/or visceral calcification with mostly mural deposits in arteries and arterioles. It is initially characterized by hyperphosphataemin followed by secondary or tertiary hyperparathyroidism. Cutaneous involvement is a rare complication. Histologically, the lesions show vascular calcification with ischaemic skin necrosis. Extreme cases may produce calcinosis cuits (calciphylaxis), i.e. disseminated calcification of the subcutaneous tissue and dermis in the form of hard painful cutaneous nodules and plaques with subsequent ulceration. Metastatic calcinosis is a disease affecting adults. While the dystrophic or idiopathic type can develop in children. We present the case of a 6-year-old boy with end-stage renal disease, attributed to congenital renal hypoplasia, and accompanied by secondary hyperparathyroidism. He developed fulminant tertiary hyper- parathyroidism and metastatic caleinosis of the lungs, as well as cutaneous neerosis of the buttocks and legs, subsequent to calcification of arteries and arterioles. A maternal renal transplant failed to function. The serum parathormone, calcium and phosphate levels could not be controlled by maintenance dialysis, phosphate binders and calcitriol. Total parathyroldectomy without auto-transplantation of parathyroid tissue rapidly returned the serum parathormone, calcium and phosphate levels to normal. In addition, topical treatment using merbromine solution and hydro- colloid dressings, healed the ulcers with significant scar formation, within 2.5 months after para- thyroidectomy. A renewed increase of the calcium x phosphate product, 2 months after parathyroidectomy, was attributed to mobilization of calcium compounds from the viseera, as confirmed by a chest X-ray.

Notes: Summary Structural hair changes may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder. We report a 22-month-old Turkish girl and her 10-month-old brother, whose scalp hair became fragile and sparse at about 6-7 months of age. Glucosuria. without diabetes or kidney disease, was detected 3-4 months later. Clinical examination revealed normal physical and mental development, and an analysis of plucked hairs showed dysplastic and broken hair shafts. Polarizing microscopy and scanning electron microscopic studies revealed torsion, and irregularities and impressions of the hair shaft, as seen in pilitorti. trichorrhexis nodosa and pseudomonilethrix. Analysis of the amino-acid composition of the hair demonstrated a significant reduction of sulphonic cysteic acid and an elevated cysteine and lanthionine content in the girl, and elevated lanthionine levels in her brother. Electrophoretic analysis of the girl's hair proteins revealed a normal composition but a high extractability of hair proteins.The triad of hypotrichosis structural hair-shaft defects and abnormal amino-acid composition, accompanied by glucosuria without diabetes, may represent a new genetic syndrome.

Notes: Several therapeutic methods have been employed in the management of localized granuloma annulare (GA), with varying degrees of success. We performed a prospective trial to evaluate the efficacy, cosmetic results, and safety of cryosurgical treatment in GA.Thirty-one patients with localized GA were treated by cryosurgery, using the contact method. Nitrous oxide (−86°C) or liquid nitrogen (–196°C) were used as refrigerants, and were applied with closed probes; each lesion was treated with one freeze-thaw cycle of 10–60s per session. If necessary, treatment was repeated after 20–30 days.Resolution of the lesions was obtained in all patients, and in 25 of 31 patients (80.6%) they resolved after a single freeze-thaw cycle. Relapse occurred in only one of 11 patients who were followed for more than 2 years, and this occurred 16 months after treatment. Excellent cosmetic results were obtained in 14 of 28 patients who were eligible for evaluation (50%), and good results in 11 (39.3%). The cosmetic result obtained by cryosurgery with nitrous oxide was independent of the size of the lesion, whereas in the group of patients treated with liquid nitrogen a better cosmetic result was obtained with smaller lesions (comparison of lesions 〈inlineGraphic alt="leqslant R: less-than-or-eq, slant" extraInfo="nonStandardEntity" href="urn:x-wiley:00070963:BJD494:les" location="les.gif"/〉2.40 cm2 with those 〉2.40 cm2; P = 0.04). The duration of the lesion, its location, previous treatment with another method, and the number of treatment sessions, did not have any influence on the cosmetic result. The treatment was generally well tolerated. Blister formation occurred in all patients. Atrophic scars occurred in four of 19 patients (21.1%), all of whom had been treated with liquid nitrogen.Cryosurgery is effective and safe in the treatment of localized GA, and excellent cosmetic results may be achieved. We propose that the use of nitrous oxide as a refrigerant, with a single freeze-thaw cycle of 20 s, covering the entire surface of small lesions and the active rim of larger lesions (〈inlineGraphic alt="geqslant R: gt-or-equal, slanted" extraInfo="nonStandardEntity" href="urn:x-wiley:00070963:BJD494:ges" location="ges.gif"/〉4 cm in diameter) is the optimal therapeutic regimen.

Notes: Facial palsy and orofacial swelling in childhood represent a challenge in differential diagnosis for paediatricians and dermatologists. One possible entity, Melkersson–Rosenthal syndrome (MRS), is a rarity in childhood. We describe a 9-year-old girl with the diagnosis of MRS who had episodic swelling of the upper lip and complete peripheral facial palsy, associated with herpes and recurrent bacterial infections. Therapeutic options for MRS in childhood are limited. Our patient benefited from a 2-month course of prednisolone 1 mg kg−1 daily. We review previously published cases of MRS in childhood, and discuss the differential diagnosis of orofacial swelling and facial palsy as well as treatment options in children.

Notes: High variability of the clinical appearance of malignant melanoma (MM) and its metastases render the differential diagnosis of solid amelanotic tumours difficult. We report a 71-year-old woman with several unusual cutaneous tumours of cerebriform morphology, suggesting skin metastases from occult internal cancer. Histopathological findings and thorough investigations, however, revealed a late-stage metastatic MM. We discuss the differential diagnosis of skin metastases of various origin and underline the difficulties for early detection of MM.

Notes: Pro-opiomelanocortin (POMC) peptides such as ACTH and α-MSH play an important role in the pigmentation of human skin and hair. Both peptides bind to a family of transmembrane receptors known as the melanocortin receptors (MC-Rs). To investigate the in situ expression of α-MSH, ACTH and MC-Rs, we performed immunohistochemical studies on human terminal and vellus hair follicles. Immunoreactivity for ACTH, MC-1R and MC-4R was detected in both human terminal and vellus hair follicles, with a pronounced increase of staining intensity in the suprabulbar and bulbar region of anagen hair follicles. The MC-1R immunoreactivity in situ was in accordance with in vitro studies showing expression of MC-1R at the RNA level in human hair follicle keratinocytes. There was no detectable difference in the staining pattern of strong, pigmented terminal hair follicles as compared with fine, silky and non-pigmented vellus hair follicles. These results indicate that POMC-derived peptides may play a regulatory role in the human hair follicle independent of the pigmentation process. The expression pattern of ACTH and its receptors MC-1R and MC-4R in the human hair follicle correlates with the immune privilege of the human hair follicle which is characterized by the absence of immune cells in the bulbar region of anagen hair follicles. Thus, ACTH may possibly be involved in the maintenance of the peribulbar immune privilege in both, terminal and vellus hair follicles.

Notes: In contrast to the well-established role of melanocortins on melanocyte function, the expression and relevance of melanocortin receptors (MC-Rs) in skin fibroblasts is incompletely understood. We recently showed that human dermal fibroblasts derived from foreskin express functional MC-1Rs which mediate an inhibitory action of α-melanocyte-stimulating hormone (α-MSH) on collagen metabolism (Böhm et al., J Biol Chem 2004, in press). Here, we show by RT-PCR, immunofluorescence, immunohistochemistry and immune electron microscopy that MC-1R expression is conserved in vitro and in vivo in additional human fibroblastic cell types of the skin including adult dermal fibroblasts, fibrosarcoma cells, connective tissue sheath fibroblasts and dermal papilla cells of the hair follicle. In vitro expression of MC-1R declines as a matter of cellular senescence in dermal fibroblasts. Interestingly, α-MSH inhibits the inductive effect of interferon-γ, an important proinflammatory mediator in inflammatory and fibrotic skin diseases, on expression of adhesion molecules such as intercellular adhesion molecule-1 in human dermal fibroblasts. These data point towards an additional biological role of α-MSH as a modulator of inflammatory reactions in the connective tissue compartment of the skin.

Notes: Pro-opiomelanocortin (POMC)-derived peptides are well-known regulators of pigmentation and proliferation of epidermal and hair follicle-derived melanocytes. We demonstrated that human dermal papilla cells (DPCs), a distinct myofibroblastic cell population of the hair follicle, participate in the cutaneous POMC system. DPCs in vitro and in situ expressed the melanocortin receptor-1 (MC-1R) as well as MC-4R as shown by RT-PCR, immunofluorescence and immunohistochemistry. Expression of POMC but not agouti signalling protein, a natural MC-1R/MC-4R antagonist, was also detectable in DPC. Generation of POMC peptides by DPCs in vitro was demonstrated by immunofluorescence and ELISA studies revealing the expression of both adrenocorticotropin and β-endorphin. To investigate the functional relevance of MC-R expression in DPCs, we examined the effect of α-MSH on interferon-γ (IFN-γ)-induced expression of intercellular adhesion molecule-1 (ICAM-1), an adhesion molecule upregulated in inflammatory disorders of the hair follicle such as alopecia areata. α-MSH markedly suppressed the IFN-γ-mediated upregulation of ICAM-1 in DPCs as shown by real-time PCR studies, while α-MSH alone did not have any effect. Our data suggest that melanocortins such as α-MSH mediate paracrine and autocrine effect in the dermal papilla whose disruption may contribute to inflammatory diseases of the hair follicle.