Implication of interleukin-4 in wound healing.

Interleukin-4 (IL-4) is a pleiotropic cytokine that is able to activate connective tissue cells and stimulate the accumulation of extracellular matrix macromolecules. In this report, the expression of IL-4 in normal wound healing was studied by immunohistochemistry. The effects of exogenous IL-4 or IL-4 antisense oligonucleotides administration were also studied in mouse experimental wounds. IL-4 expression was detected in the lower dermis below the wound as early as Day 1 after wounding. IL-4 expression was maximal by Day 4, then decreased progressively, and completely disappeared by Day 21 after wounding. Topical administration of IL-4 on experimental wounds in mice significantly accelerated the rate of healing, whereas IL-4 antisense oligonucleotides significantly inhibited healing. These results demonstrate that IL-4 may be implicated in normal wound healing.

[Cutaneous actinomycosis in the perianal area and buttocks]. / Actinomycose cutanée péri-anale et fessière.

INTRODUCTION: Actinomycosis is a rare spreading suppurative and granulomatous disease. In 50 to 60 p. 100 of cases, cervico-facial area is involved. Involvement of other cutaneous areas is very uncommon. CASE-REPORTS: Two men (51 and 58 year-old, respectively) were admitted to the hospital because of erythematous and violaceous nodules with fistulization to the skin, localized on the perianal area and buttocks for several months. Bacterial cultures of the pus and of skin biopsy specimens yielded Actinomyces meyeri in case 1 and Actinomyces israelii in case 2. Patients did not have other infectious lesions. Treatment included systemic antibiotics and surgical iterative excisions in case 1. DISCUSSION: The main interest of those two cases is their similar clinical presentation and in one case the rarity of the micro-organism involved (Actinomyces meyeri). Since the lesions involved only the skin, we postulate that the organism may have extended from the oral mucosa through the gastrointestinal tract.

[Cryosurgery of basal cell carcinoma: a study of 358 patients]. / Cryochirurgie des carcinomes basocellulaires: étude de 358 malades.

INTRODUCTION: Cryosurgery is a well-established therapeutic modality for basal cell carcinoma. We report herein an important series of basal cell carcinoma treated by cryosurgery, with a five year cure rate evaluation. PATIENTS AND METHOD: Retrospective study with 395 basal cell carcinomas (over 358 patients - sex ratio H/F: 0.85) treated by cryosurgery between 1981 and 1992. For each patient the data were: age, sex, size of the lesion, location, clinical sub-type, tissue-temperature monitoring, recurrence date and esthetic outcome. RESULT: The lesions were located on the face (93 p. 100) and back (7 p. 100). Mean size was 17 mm. Clinical sub-types were known for 178 lesions; 11 p. 100 of BCC were morpheaform. Tissue-temperature monitoring was performed for 55 p. 100 of cases. 111 tumors were observed for more than 5 years. The 5-year actuarial failure rate was 9 p. 100. The 5-year cure rate was not significantly altered by sex, size of lesions, location and clinical sub-type. No frequent recurrences were observed when tissue-temperature monitoring had not been performed. Complications were rare and esthetic outcome was good. DISCUSSION: The 5-year actuarial recurrence rate with cryosurgery is similar to conventional surgery. It is not essential to control tissue-temperature for preventing recurrences. Cryosurgery is a reliable treatment and outcome depends on surgeon experience. Quickness and low cost of this procedure argue for choosing cryosurgery when treating elderly patients.

[Secondary cutaneous effects of hydroxyurea: prospective study of 26 patients from a dermatologic consultation]. / Effets secondaires cutanés de l'hydroxyurée: étude prospective de 26 patients consultant dans un service de dermatologie.

PURPOSE: Hydroxyurea is a treatment of myeloproliferative syndromes. Its cutaneous side-effects are underestimated, because they are usually benign. We undertook a prospective study to evaluate their frequency. METHODS: During a 2-year period, all patients taking hydroxyurea for more than 6 months who had consultations at the dermatology department were systematically examined, regarding cutaneous side effects. RESULTS: Twenty-six patients were examined. All but one had cutaneous side-effects, including dryness (n = 16), moderate alopecia (n = 2), increased skin pigmentation (n = 5), melanonychia, single (n = 1) or multiple (n = 7), cutaneous atrophy (n = 4), leg ulcers (n = 8), plantar keratoderma (n = 3), pseudodermatomyositis (n = 1), lichen planus-like eruption on the dorsum of the hands (n = 2), actinic keratosis (n = 8), squamous cell carcinomas (n = 2), and mouth ulcerations (n = 1). CONCLUSION: This study shows that the frequency of hydroxyurea cutaneous side-effects diagnosed in 95% of studied patients is underestimated. They are usually benign, but some of them, in particular leg ulcers and squamous cell carcinomas, lead to modification of the treatment (39% of studied patients).

[Acute generalized exanthematous pustulosis in hypercalcemia]. / Pustulose exanthématique aiguë généralisée d'une hypercalcémie.

BACKGROUND: We report a case of typical exanthematous pustulosis rash that was particularly severe both clinically and biologically. Laboratory tests led to the diagnosis of acute parvovirus B19 infection. CASE REPORT: A 23-year-old man with no past medical history developed fever with an erythematous pustulosis rash predominantly involving the folds. Blood cell count revealed hyperleukocytosis. There was no previous drug intake. This skin reaction was associated with severe systemic manifestations including hypovolemic shock, and hematologic and metabolic disturbances. Virology tests revealed acute parvovirus B19 infection. The hospital physician caring for this patient also presented evidence of acute parvovirus B19 infection. DISCUSSION: The clinical features and the course of this skin eruption were typical of generalized exanthematous pustulosis. We discuss the rare viral causes of acute generalized exanthematous pustulosis and compare our case with a previously reported case of acute generalized exanthematous pustulosis with mononucleosic syndrome in a patient with no prior drug intake. The clinical and biological manifestations of this case were similar to drug hypersensitivity syndrome.

[Secondary longitudinal melanonychia secondary to onychophagia]. / Mélanonychies longitudinales secondaires à une onychophagie.

BACKGROUND: Melanonychia of the toenails sometimes results from repeated trauma. This etiology is rarely put forward in lesions affecting the fingernails. CASE REPORT: A 44-year-old woman developed melanonychia affecting 9 fingernails. Genetic predisposition and drug, hormonal or infectious causes were ruled out and we postulated that the lesions were induced by nail biting. DISCUSSION: Nail biting is known to lead to several types of lesions, including melanonychia. The lesions may sometimes disappear several months after stopping this habit.

Recurrent painful hand crisis in a four-year-old girl, revealing an erythropoietic protoporphyria.

We report the case of a 4-year-old girl, who had been suffering for 2 years from a recurrent, painful crisis affecting both hands, following sun exposure. There were no obvious cutaneous lesions, which initially caused us to consider a diagnosis of a psychiatric disorder. However, the diagnosis of erythropoietic protoporphyria was then established by the demonstration of elevated levels of free protoporphyrin in erythrocytes. The present case illustrates the effectiveness of beta-carotene associated with canthaxanthin in erythropoietic protoporphyria.

Palmoplantar filiform hyperkeratosis with Darier's disease. Association or coincidence?

Palmoplantar orthokeratotic filiform hyperkeratosis is characterized by multiple, spiny, keratotic projections. We report a new case, occurring in an 85-year-old woman, associated with typical Darier's disease involving her chest and groin, that may be not fortuitous. Three previous reports point out its possible association with underlying diseases, such as malignancy or Darier's disease.

[Multiple isolated cutaneous myxomas]. / Myxomes cutanés multiples isolés.

INTRODUCTION: Cutaneous myxomas are rare. They are more often single; when they are multiple, they may be one of the component of the Carney's syndrome. CASE REPORT: We report a case of multiple and isolated cutaneous myxomas arising at 19 year-old. Diagnosis was confirmed by histologic studies. Examination failed to reveal other cutaneous or visceral features. DISCUSSION: The multiplicity of cutaneous myxomas is an essential element for diagnosis of Carney's syndrome; other components and notably atrial myxomas can appeared over time. Normal visceral explorations don't eliminated the diagnosis, and follow-up including screening echocardiography must be ensured before concluding, as in our case, as multiple and isolated cutaneous myxomas.

[Chronic depigmentation due to positive patch tests for methacryate derivatives]. / Dépigmentation durable secondaire à des tests positifs aux dérivés des méthacrylates.

INTRODUCTION: Many chemical products are known to induce depigmentation. This phenomenon was never reported with methacrylates which are components of acrylic resine. CASE REPORT: A female patient with artificial nails developed contact dermatitis. Localized depigmentation at the site of positive patch tests to methacrylates derivatives was observed. DISCUSSION: The chemical substance could have a direct influence either by its toxic effect or by the induced inflammatory reaction.

A comparative study of cryogenic lesions in organ-cultured human skin and in reconstituted human skin equivalent.

Cryosurgery is a technique that is widely used in the treatment of cutaneous tumors. However, there are still features of healing in cryosurgery wounds that are incompletely understood and necessitate further study. In the present paper, we describe two in vitro models that were developed to study the initial stages of development of the cryolesion: reconstituted human skin and organ-cultured human skin. Cryolesions were generated in both models by applying a 2-mm-diameter cryoprobe at -196 degrees C for 35 s. Histological features were analyzed at days 0, 3, 5, and 14 following cryotreatment and showed epidermal detachment and keratinocyte necrosis very close to the findings reported in vivo. Results were similar in the two models. Gross alteration of the dermal architecture was noticed beneath the cryolesion, particularly in the reconstituted skin model. Cell proliferation was investigated at days 0, 3, and 5 by [3H]thymidine incorporation and Ki-67 antigen immunolabeling. In the case of organ-cultured skin, a significant increase in keratinocyte and fibroblast proliferation was observed at day 3, compared to the controls. At day 5, a return to the basic level was noticed. This was not observed in the reconstituted skin model at either day 3 or day 5. These data led us to propose that organ-cultured skin may be a useful model for evaluating the response of human skin to freezing; reconstituted skin was not adequate for this purpose.

Antagonistic effects of interferon-gamma and interleukin-4 on fibroblast cultures.

A major characteristic of scleroderma (SSc) fibroblasts is an increased biosynthesis of extracellular matrix macromolecules that could be linked to impaired regulation by cytokines. We investigated the effects of two cytokines from T lymphocytes, interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), on normal and scleroderma fibroblast cultures. In both types of fibroblasts, IL-4 strongly stimulated collagen synthesis, whereas IFN-gamma was a potent inhibitor. The effects of these cytokines were localized at the pre-translational level, and both mRNA steady-state level and protein synthesis were equally affected. SSc fibroblasts responded to IL-4 and IFN-gamma as well as normal fibroblasts. When fibroblasts were incubated with combinations of both cytokines, IFN-gamma completely suppressed the stimulation of collagen gene expression induced by IL-4. Northern blot and western blot analyses demonstrated that IFN-gamma induced a rapid and strong decrease in the expression of the IL-4 receptor-alpha by fibroblasts. This effect might explain the antagonistic effects of IFN-gamma on the IL-4-dependent enhancement of collagen synthesis. Thus, our data suggest that the alteration of collagen production in scleroderma fibroblasts does not depend on an altered sensitivity of these cells to stimulatory or inhibitory cytokines but is more likely the consequence of an imbalance in the local production of autocrine or paracrine regulatory factors.

[Palmoplantar filiform parakeratotic hyperkeratosis and digestive adenocarcinoma]. / Hyperkératose palmo-plantaire filiforme parakératosique et adénocarcinome digestif.

INTRODUCTION: There are very few observations of filiform palmo-plantar hyperkeratosis reported. Nevertheless it's worth knowing this entity for his potential association with a visceral neoplasia. CASE REPORT: We report the first case of filiform palmo-plantar hyperkeratosis associated with a digestive adenocarcinoma and a polycystic kidney disease. DISCUSSION: After a review of palmar and plantar filiform hyperkeratosis in the literature, we will discuss the possible association with neoplasia or other pathologies. This pathology requires a strict clinical and paraclinical follow-up.

Expression of interleukin-4 in scleroderma skin specimens and scleroderma fibroblast cultures. Potential role in fibrosis.

BACKGROUND: Scleroderma (systemic sclerosis) is a fibrotic disease characterized by an uncontrolled tissular accumulation of collagen. Several cytokines have been implicated in the fibroblast activation leading to fibrosis. For instance, we have previously demonstrated that interleukin-4 (IL-4) is a potent activator of collagen synthesis in fibroblast cultures. In this study, using immunocytochemical methods and in situ hybridization, we investigated the expression of IL-4 in normal and scleroderma skin and fibroblast cultures. OBSERVATIONS: Immunocytochemical studies with anti-IL-4 antibody were performed on biopsy specimens from 9 patients with normal skin and 11 patients with scleroderma. The label was intense or strong in 8 of the 11 scleroderma skin specimens, whereas it was negative or faint in 8 of the 9 normal skin specimens (P < .01). In situ hybridization demonstrated a significant increase of the number of IL-4 messenger RNA grains in scleroderma skin compared with normal skin (3.1 +/- 1.5 [mean +/- SD] vs 0.8 +/- 0.7; P < .001). A strongly positive labeling with the anti-IL-4 antibody was found in the 4 scleroderma fibroblast cultures, whereas it was negative in the 5 fibroblast control cultures (P < .05). CONCLUSIONS: Our results demonstrate that IL-4 is strongly expressed in the dermis of a large majority of patients with scleroderma and might be synthesized by scleroderma fibroblasts. We suggest that IL-4 is one of the cytokines implicated in the early steps of the fibrotic process.

[Unilateral gustatory flushing syndrome in a child]. / Syndrome des flushs gustatifs unilatéraux de l'enfant.

BACKGROUND: Auriculo-temporal syndrome is rarely seen in children: it is sometimes considered as secondary to an obstetrical injury. CASE REPORT: A 2.5 year-old boy was examined because he suffered from post-prandial flushing of the right cheek for 2 years. He was born normally and neurologic examination was normal. The rash was not associated with sweating or tearing. CONCLUSION: There is no evidence to support food allergy in this case: rather, this syndrome probably occurs in response to salivation.

[Vulvar lymphangiectasis 14 years after treatment for epidermoid carcinoma of the cervix. Treatment with cryosurgery]. / Lymphangiectasies vulvaires 14 ans après le traitement d'un carcinome épidermoïde du col utérin. Traitement par cryochirurgie.

INTRODUCTION: Lymphangiectasia are different from lymphangioma because they arise following damage to the deeper lymphatic vessels. No clinical or histological features are known to distinguish lymphangioma from lymphangiectasia. CASE REPORT: We report a case of vulvar lymphangiectasia occurring 14 years after therapy of squamous carcinoma of the cervix (surgery and post-operative radiotherapy). Our treatment was cryosurgery. DISCUSSION: We analysed the 12 case reports of vulvar lymphangiectasia in the literature, emphasizing misleading clinical aspect of the warty lesions and the risk of repeated infection justifying an appropriate treatment. We propose cryosurgery which provides real benefits with a minimal trauma.