Prolonged healing of venous leg ulcers: the role of venous reflux, ulcer characteristics and mobility.

OBJECTIVE: To assess whether a difference in venous reflux pattern, ulcer size or duration, regular medications or the daily use of walking aids can predict the healing of a chronic venous leg ulcer (VLU). METHOD: In this prospective, randomised, single-centre study, 110 consecutive patients with chronic leg ulcers were assessed. Ninety-nine patients met the inclusion criteria and a controlled, conservative 3-month treatment period was initiated, in which 90 patients were managed with standardised local treatment combined with compression therapy. In this group, 62 VLUs healed within 12 weeks and 28 were still open after 12 weeks. The study group consisted of 22 patients with non-healed ulcers and a control group (n=28), which was selected randomly from the healers. In both groups, venous reflux profiles were assessed using colour-flow duplex imaging. RESULTS: The study and control groups did not differ in smoking habits, age, gender or daily oral medications. On average, the healing wounds were 5cm² before starting controlled treatment (range 1-80cm²) and had been open for 7 months (range 2-48 months); the non-healing wounds were on average 11.2cm² (range 1-31cm²) and had been open for 26 months (range 8-106 months). Venous disease severity scores were similar for both groups (12.6 vs. 13.4). Five patients (18%) with healed ulcers regularly used walking aids, the use of which was more frequent (36%) among non-healers (p<0.001). Venous reflux profiles differed significantly between the groups, with isolated superficial reflux noted in 64% of healers, compared with 36% of non-healers. In addition, isolated deep reflux was found in 14% of the healers, compared with 41% of non-healers (p=0.0002). The rate of popliteal reflux was significantly higher in non-healers (59% versus 21%; p=0.0004). CONCLUSION: Long duration of a chronic venous ulcer may predict a poor outcome. The presence of deep venous reflux, especially in the popliteal vein, is typically found in those legs with non-healed ulcers. .

Pinch grafting of chronic leg ulcers: a retrospective analysis of 104 patients with 169 ulcers.

OBJECTIVE: To compare healing rates of inpatients and outpatients with chronic leg ulcers treated with pinch grafting and to define which of these patients would benefit most from the therapy. METHOD: This retrospective analysis reports the healing rates of 104 patients with 169 ulcers treated with pinch grafting during 1997-2007 at the Department of Dermatology, Tampere University Hospital. RESULTS: These relate to 17 outpatients with 18 pinch-grafted ulcers and 95 inpatients with 151 ulcers. Nine ulcers (50%) in the outpatient and 95 (62.9%) in the inpatient group healed completely. Median healing times were five and eight weeks for the outpatient and inpatient groups respectively. For the sample as a whole, 61.5% of the ulcers healed. CONCLUSION: This retrospective study found that pinch grafting is an efficient method of treating chronic leg ulcers, with an overall healing rate over 60%. Patients who complied with compression therapy were most likely to benefit from this therapy.

Eosinophilic pustular folliculitis.

Eosinophilic pustular folliculitis is a rase dermatosis and the treatment is difficult because the underlying pathogenic mechanism is unknown. The authors report a case of eosinophilic pustular folliculitis (Ofuji's disease) in a 50-year-old man who died 9 years after onset of the disease.

Treatment of mosquito bites with ebastine: a field trial.

Wealing and pruritic, long-lasting papules are a common nuisance from mosquito bites. Antihistamines can be expected to decrease wealing, but their effect on the delayed bite symptoms needs to be elucidated. We studied the effect of ebastine in 28 mosquito-bite sensitive adult subjects exposed to Aedes communis bites in the field. Ebastine 20 mg and placebo were given for 4 days in a cross-over fashion, and the size of the bite lesion and the intensity of pruritus (visual analogue scale) were measured at 15 min and 2, 6 and 24 h after the bites. Ebastine decreased significantly (p <0.001) the size of the bite lesion and pruritus at 15 min. Ebastine also had a significant effect (p<0.01) on pruritus at 2 and 24 h, and this effect was highly significant when the measurements at all 4 time points were pooled. Five patients (18%) on ebastine, but none on placebo, experienced sedation (ns). The present field study shows that ebastine 20 mg given prophylactically is effective against immediate mosquito bite symptoms, and that it also significantly decreases pruritus associated with the delayed bite papules.

Adequate blood flow is essential for reinnervation in neurovascular skin flaps.

The effect of arterial and venous ischaemia on reinnervation of skin flaps after transsection and resuture of the epigastric nerve was investigated in rat groin flaps. The results were compared with those in corresponding flaps with adequate blood flow. Arterial or venous ischaemia was induced by ligation of the epigastric artery or vein. The reinnervation of the flaps was studied after a 20-week healing period using specific antisera for calcitonin gene-related peptide (CGRP) in sensory nerves, and neuropeptide Y (NPY) in adrenergic nerves. Arterial ischaemia clearly and significantly hampered reinnervation. Venous ischaemia was even more harmful and practically no regenerated nerves were detected in the flaps. We conclude that adequate blood flow is critical for sensory and adrenergic reinnervation in skin flaps.

Reinnervation after nerve suture in rat groin flaps.

Regeneration of sensory and adrenergic nerves in the skin was studied in rats. The aim was to investigate the effect of reanastomosing the cut nerve ends of the nerve trunk leading to the microvascular groin flap. Reinnervation was demonstrated immunohistochemically using calcitonin gene-related peptide (CGRP) as marker for sensory nerves, neuropeptide Y (NPY) and tyrosine hydroxylase (TH) as markers for adrenergic nerves and Protein Gene Product 9.5 (PGP 9.5) as general neuronal marker. It was demonstrated that reanastomosing of the nerve trunk was favourable for both the sensory and sympathetic reinnervation of microsurgical flaps.

Effect of cetirizine on the inflammatory cells in mosquito bites.

BACKGROUND: Mosquito bites frequently cause wealing and delayed papules which appear within a few hours after the bites and may persist for several days. Cetirizine is an effective drug against mosquito bites by decreasing wealing and also the size and pruritus of the delayed bite papules. OBJECTIVES: To characterize inflammatory cells in the delayed mosquito-bite lesions, and to study the effect of cetirizine on the inflammatory cell response. METHODS: Twenty-six mosquito-bite sensitive subjects received cetirizine 20 mg (14 subjects) or placebo (12 subjects) in a double-blind fashion. Aedes aegypti-bites were given on a forearm and serial punch biopsies were taken at 2-, 6- and 24h after the bite exposure. Eosinophils, neutrophils, mast cells, mononuclear cells and T- helper (CD4+) and suppressor (CD8+) lymphocytes were counted from dermal infiltrates. RESULTS: Eosinophils and neutrophils were found already in 2-h bite lesions. Moreover, the number of mononuclear and CD4+ cells increased significantly (P < 0.01) from 2- to 24-h bite lesions. Unexpectedly, the overall numbers of eosinophils (P < 0.05), mononuclear cells (P < 0.01) and CD4+ cells (P < 0.01) were significantly higher in the cetirizine-treated subjects compared with the placebo-treated subjects. CONCLUSIONS: The results suggest that the inflammatory cell response in the delayed mosquito-bite lesions is similar to that occurring in allergic late-phase responses, i.e. an early influx of eosinophils, neutrophils and subsequent accumalation of CD4+ lymphocytes. The reason for the high numbers of eosinophils and CD4+ cells in the cetirizine-treated subjects is not known.

Expression of diazepam-binding inhibitor peptide in human skin: an immunohistochemical and ultrastructural study.

Human diazepam binding inhibitor (DBI) was originally isolated from the brain and subsequently found to be present in several peripheral tissues. The various physiologic effects recently attributed to DBI include acting as an endogenous ligand for the central and peripheral (mitochondrial) benzodiazepine receptors. The present work provides, for the first time, evidence of DBI immunoreactivity in skin. DBI immunoreactivity was found in the epidermis, in the eccrine sweat and in sebaceous glands. Ultrastructurally, DBI was distributed throughout the cytoplasm. Although the physiologic role of DBI in skin is unknown, our results indicate that DBI may serve as an endogenous ligand for mitochondrial benzodiazepine receptors. Its activity could be related to the regulation of lipid and cholesterol synthesis in keratinocytes and sebaceous glands and to the secretion of sweat in sweat glands.

Systemic corticosteroid and isotretinoin treatment in cystic acne.

Prednisolone combined with erythromycin was given to 6 patients with cystic acne. The treatment responses were compared to those in 6 patients with cystic acne receiving isotretinoin and erythromycin and also to those in 3 patients with acne fulminans treated with prednisolone and erythromycin. During the first 4 weeks cystic acne showed a clear improvement in 5 out of 6 patients in both treatment groups. A similar improvement occurred in all 3 patients with acne fulminans. When corticosteroid was stopped, 2 out of 5 patients with cystic acne had a relapse and needed isotretinoin for complete control. In the isotretinoin-treated group, one patient with cystic acne needed prednisolone because the acne worsened to an ulcerative form. Slightly elevated liver enzymes, possibly due to erythromycin treatment, were observed in 2 patients with cystic acne and in one patient with acne fulminans. The present results show that prednisolone combined with erythromycin is an effective treatment during the early stages of cystic and febrile acne, but isotretinoin is needed for long-term control.

Location of androgen receptor in human skin.

The distribution of androgen receptor (AR) in human skin was studied by an immunohistochemical method using a polyclonal antibody against the human AR. Skin samples of preputial skin and male and female nongenital skin were examined. The possible correlation of AR location to acne was studied in skin biopsies from skin areas affected or unaffected by acne. In preputial skin, AR was expressed in epidermal cells as well as in fibroblasts, smooth muscle cells, and endothelial cells of blood vessels in the dermal area. AR was found located also in the flat fibroblast-like cells of Pacinian corpuscles. In nongenital skin, AR was also expressed in the basal cells and glandular cells of sebaceous glands, in the outer root sheath of hair follicles, and in eccrine sweat glands. The presence of AR in different cell types in the skin reflects the numerous direct effects androgens may have on this target tissue. The distribution of AR was similar in male and female skin.

Evidence for gamma-melanocyte stimulating hormone containing nerves and neutrophilic granulocytes in the human skin by indirect immunofluorescence.

gamma-melanocyte stimulating hormone (gamma-MSH)-like immunoreactivity has been found by indirect immunofluorescence in nerve fibers and terminals as well as in neutrophilic granulocytes of normal human skin. A preferential localization to sensory nerves was seen; abundant nerve fibers displaying gamma-MSH immunoreactivity were observed as free nerve endings in the basal layer of the epidermis and in the upper dermis, close to the Merkel cells, in Meissner's corpuscles, around the external root sheath of the lower part of the hair follicles, and in nerve bundles of the deeper parts of the dermis. Very few fibers were seen to be associated with sweat glands and most blood vessels, although arterioles were densely innervated. Thus, gamma-MSH should be considered for possible role as a sensory or axon-reflex chemical messenger. Furthermore, the presence of gamma-MSH in neutrophilic granulocytes raises the possibility that gamma-MSH may play a role in the genesis of post-inflammatory hyperpigmentation, nevi, and melanomas.

Neuropeptides in cutaneous neurofibromas of von Recklinghausen's disease.

The occurrence of neuropeptides was studied in neurofibromas of von Recklinghausen's disease by indirect immunofluorescence. All non-plexiform cutaneous neurofibromas contained abundant vasoactive intestinal polypeptide, peptide histidine-isoleucine and calcitonin gene-related peptide immunoreactive nerves. The nerves were small and unmyelinated. Neuropeptides might be responsible for itch that occurs especially in small cutaneous neurofibromas. Neuropeptides are also suggested to act as modulators and/or trophic factors for neurofibroma growth.