FGFR2 signaling and the pathogenesis of acne

Acne in Apert syndrome and unilateral segmental acneiform nevus are associated with mutations of fibroblast growth factor receptor 2 (FGFR2), which are likely to be involved in the pathogenesis of acne. Translational animal and cellular models, developmental biology studies and clinical observations have contributed to our understanding of FGF‐FGFR2 signaling in the pilosebaceous follicle. The importance of FGF‐FGFR2 signaling in mesenchymal‐epithelial interaction for skin appendage formation, pilosebaceous follicle homeostasis, come‐dogenesis and sebaceous gland proliferation is explored. Overstimulation of FGFR2 signaling with increased expression of interleukin‐1α explains acne in Apert syndrome und nevus comedonicus. Androgen‐mediated up‐regulation of FGFR2 signaling could be the initiating signal in the pathogenesis of acne. The gain of function FGFR2 mutations in Apert syndrome and unilateral acneiform nevus are most helpful model diseases for uncovering the fundamental process of androgen‐dependent mesenchymal‐epithelial FGF‐FGFR2 signaling in acne in Apert syndrome, nevus comedonicus and acne vulgaris.     

Childhood acne. Clinical expression, etiology, and relationship to juvenile acne

Childhood acne has different clinical expressions which may be present from birth or manifest within the first weeks of life or after the third to sixth month of life. The condition may occur as a physiological phenomenon or may be pathological and require endocrinologic evaluation and treatment. It may be induced by drugs or ointments or due to intoxication. Severe courses with a tendency to scarring in childhood may be observed. Childhood acne may persist and develop into juvenile acne. It is likely that childhood acne may represent a risk factor for the development of severe acne in puberty.     

Postmenopausal acne.

Postmenopausal acne originates at or after menopause in darker-skinned, formerly oily-skinned, large-pored women who usually did not experience adolescent acne. It is a low-grade, long-smoldering acne in which small closed comedones are dominant, among which there is a scattering of dimunitive papulopustules. There is a seeming association with chin and upper lip hirsutism. Topical tretinoin is an effective therapy. Unopposed adrenal androgens present after ovarian failure may be the chief causes of this condition.     

痤疮与胰岛素抵抗相关性的研究进展

痤疮是好发于青春期的毛囊皮脂腺慢性炎症性疾病,激素是痤疮发生的最重要内源性因素。近年来发现,除雄激素外,胰岛素抵抗及其诱导的胰岛素和胰岛素样生长因子1水平异常也与痤疮密切相关,胰岛素与胰岛素样生长因子1通过间接刺激雄激素分泌、直接诱导角质形成细胞增殖和皮脂腺细胞脂质分泌以及炎症过程参与痤疮发生。此外,痤疮作为某些系统性疾病或综合征如多囊卵巢综合征、高雄激素血症?胰岛素抵抗?黑棘皮病综合征的重要特征以及饮食、吸烟、肿瘤与痤疮的相关性也为胰岛素抵抗在痤疮发生中的潜在作用提供了依据。     

Isotretinoin treatment of acne in a patient with Apert syndrome

Apert syndrome is an autosomal dominant disease caused by mutations in fibroblast growth factor receptor (FGFR-2) and characterized by premature fusion of the cranial sutures and early epiphyseal closure. The development of widespread, severe, pustular acne around puberty is a characteristic feature in these patients. The FGFR-2 mutation of Apert syndrome has been described in localized nevoid acne lesions, which have been attributed to somatic mosaicism. Isotretinoin has been reported to be useful in controlling this acne. We report the successful treatment of acne with isotretinoin in a teenager with Apert syndrome and review the pathophysiology of acne in this syndrome.     

Androgen excess in women with acne alone compared with women with acne and/or hirsutism

Acne is known to be one of the features of hyperandrogenism. The aim of the present work was to study women with persistent acne and without other evidence of hyperandrogenism, such as hirsutism, alopecia, or irregular menses. Among 87 female patients with acne and/or hirsutism, we defined three groups: group 1 (n = 29), patients having treatment-resistant acne without menstrual disturbance, alopecia, or hirsutism; group 2 (n = 27), patients with acne and hirsutism; and group 3 (n = 31), patients with hirsutism alone. Clinical chemistry criteria for hyperandrogenism were based on elevated values of one or more of the following parameters: plasma testosterone, delta-4-androstenedione, dehydroepiandrosterone, urinary 5 alpha-androstane 3 alpha-17 beta-diol, and 17-ketosteroids (with chromatography). Plasma and urine samples were drawn between the 18th and 25th days of the cycle. Among group 1 patients, we found 25 subjects (86%) with hyperandrogenism, according to these laboratory criteria. The etiologies were: polycystic ovary syndrome (36%), adrenal hypersecretion (40%, of which 12% showed secondary polycystic ovaries), isolated increase in 5 alpha-androstane 3 alpha-17 beta-diol (20%), and hyperandrogenism without diagnosis (4%). The parameters were found to be more elevated in these patients than in a control group of 30 normal volunteer women. In groups 2 and 3, the findings were essentially the same as in group 1, except for increased levels of testosterone and the testosterone/SHBG ratio. Furthermore, it was evident that persistent acne may be an isolated sign of hyperandrogenism.     

儿童期痤疮

根据发病年龄可将儿童期痤疮分为新生儿痤疮、婴儿痤疮、学龄前儿童痤疮、青春期前痤疮。新生儿痤疮和婴儿痤疮可作为青春期严重痤疮的预测因素,学龄前儿童痤疮可能与潜在内分泌疾病有关,青春期前痤疮是青春期成熟的迹象。儿童期痤疮的治疗方案和青春期痤疮相似,同时需考虑药物的不良反应和对生长发育的影响。     

Lymphocyte transformation in subjects with nodulo-cystic acne

Patients with severe nodulo-cystic acne are known to have elevated serum antibody levels and increased immediate hypersensitivity reactions to Propionibacterium acnes. This organism is the predominant bacterium in normal pilosebaceous follicles of human skin, and can be consistently isolated from pustular lesions in acne. Previously it had been observed that delayed cutaneous hypersensitivity reactions to P. acnes were negative in patients with acne. The present study investigated the proliferative response of lymphocytes from patients with nodulo-cystic acne to phytohaemagglutinin (PHA) and P. acnes antigen stimulation. The response to PHA stimulation was within normal limits. The response to P. acnes antigen showed a significant increase over control values obtained by testing lymphocytes from acne-free subjects. Thus cell mediated immunity to P. acnes may be present in subjects with severe inflammatory acne. These findings raise the possibility that reactions to P. acnes may contribute to intensifying the inflammatory response in acne lesions.     

Sweet's syndrome complicating isotretinoin therapy in acne

BACKGROUND: We report a case of juvenile acne aggravated in the form of Sweet's syndrome by isotretinoin treatment. The late onset of ulcerative-hemorrhagic rectocolitis in this patient raised doubts about a possible relationship between Sweet's syndrome, acne and inflammatory colitis. PATIENTS AND METHODS: A 19 year-old male patient with no disease history of note was treated for juvenile polymorphous acne resistant to standard topical acne treatment using isotretinoin (Roaccutane) at a dose of 0.5 mg/kg/d. After one week of treatment, the patient presented a fever of 38.5 degrees C, joint pain and congestive, erythematous-edematous, maculopapular plaques in ring-like layout subsequently becoming pustular and necrotic. These lesions occurred on the face, neck and pinna of the ear. Some nodules were also noted on the lower limbs. Biological tests and histology examination of a skin biopsy were evocative of Sweet's syndrome. The outcome was rapidly favorable following discontinuation of isotretinoin and institution of systemic corticosteroids (0.5 mg/kg/d). Two years later, ulcerative-hemorrhagic rectocolitis was diagnosed with episodes of bloody diarrhea. DISCUSSION: Treatment of acne with isotretinoin can occasionally induce inflammatory episodes of acne. To date there have been no reported cases of isotretinoin-induced Sweet's syndrome. The subsequent onset of ulcerative-hemorrhagic rectocolitis provides an indication of the complexity of the pathogenic mechanisms involved.     

Treatment of acne scarring

Background Post‐acne scarring remains a common entity despite advances in the treatment of acne. This represents limitations in our quality of therapy and a failure of public education. The level of severe scarring remains as much an ongoing challenge to prevent as well as manage. Methods This review will concentrate on the methods by which acne scarring may be improved and the available evidence for their utility. It will also rely on a grading scale of disease burden to classify patients and their ideal therapy. New therapies allowing treatment of scarring in areas other than the face will also be highlighted. Results Tabulated treatment planning will present algorithms summarizing best practice in the treatment of post‐acne scarring. Conclusion Post‐acne scarring is being better managed. Grade 1 scars with flat red, white, or brown marks are best treated with topical therapies, fractionated and pigment or vascular‐specific lasers and, occasionally, pigment transfer techniques. Grade 2 mild scarring as seen primarily in the mirror is now the territory of non‐ablative fractionated and non‐fractionated lasers as well as skin rolling techniques. Grade 3 scarring, visible at conversational distance but distensible, is best managed by traditional resurfacing techniques or with fractional non‐ablative or ablative devices, sometimes including preparatory surgical procedures. Grade 4 scarring, where the scarring is at its most severe and non‐distensible, is most in need of a combined approach.     

Cystic acne and clinocomptodactyly in Klinefelter's syndrome (46XY/47 XXY mosaic)

Klinefelter's syndrome was found in a 18 year old patient, suffering for four years from nodulocystic acne. Serum gonadotropins were within normal range, while histology of the testes revealed beginning tubular hyalinization. The case report shows that young patients with Klinefelter's syndrome may present symptoms that seem to exclude this syndrome. Furthermore, our patient exhibited klinokamptodaktylia of hands and feet, a congenital anomaly occurring very rarely in Klinefelter's syndrome.     

Neonatal acne vulgaris: a possible feature of the fetal hydantoin syndrome

A baby with the fetal hydantoin syndrome was found to have acne vulgaris of the face. Hydantoin taken by epileptic women during pregnancy may cause neonatal acne in the offspring.     

Postadolescent acne in women.

A low-grade, persistent acne is quite common in hard-working professional women in their twenties, thirties, and forties. Closed comedones are the dominant lesions, with a scattering of papulopustules. Premenstrual flares are typical. Most such patients passed through adolescence without acne. Acne cosmetica has to be ruled out. The latter is more inflammatory and the lesions are denser. It is postulated that chronic stress leads to enhanced secretion of adrenal androgens, resulting in sebaceous hyperplasia and subsequent induction of comedones. Postadolescent acne is an authentic variety of acne vulgaris; it responds well to treatment with conventional topical medicaments.     

Successful acne management in Apert syndrome twins

Abstract:  Apert syndrome, or acrocephalosyndactyly, is characterized by craniosynostosis and early epiphyseal closure resulting in various deformities of the skull, hands, and feet. Typically a sporadic condition, autosomal dominant inheritance with complete penetrance has been known to occur. Most adolescents with the disorder are prone to the development of severe pustular facial and truncal acne, with extension to the upper arms and forearm. We report twin brothers with Apert syndrome who, after 2 years of standard management by their pediatrician, were referred for management of complicated acne. In our patients there were a constellation of findings consistent with the disorder and, of importance to this report, significant dermatological manifestations. On presentation, each brother was found to have acne vulgaris of a different stage. Our patients were refractory to conventional treatment for acne but one required and had a significant response to isotretinoin. The risk/benefit ratio in treating acne lesions with isotretinoin in a teenager with Apert syndrome is reviewed.     

Genetic architecture of acne vulgaris

Acne vulgaris is a ubiquitary skin disease characterized by chronic inflammation of the pilosebaceous unit resulting from bacterial colonization of hair follicles by Propionibacterium acnes, androgen‐induced increased sebum production, altered keratinization and inflammation. Here, we review our current understanding of the genetic architecture of this intriguing disease. We analysed genomewide association studies (GWAS) and candidate genes studies for acne vulgaris. Moreover, we included GWAS studies for the associated disease polycystic ovary syndrome (PCOS). Overall, the available data revealed sixteen genetic loci flagged by single nucleotide polymorphisms (SNPs), none of which has been confirmed yet by independent studies. Moreover, a GWAS for PCOS identified 21 susceptible loci. The genetic architecture is complex which has been revealed by GWAS. Further and larger studies in different populations are required to confirm or disprove results from candidate gene studies as well to identify signals that may overlap between different populations. Finally, studies on rare genetic variants in acne and associated diseases like PCOS may deepen our understanding of its pathogenesis.     

The frequency of polycystic ovary syndrome in females with resistant acne vulgaris

Background Acne vulgaris in females may be resistant to treatment in spite of topical and systemic therapy for a sufficient period. In this condition, acne may be a manifestation of underlying endocrine conditions such as polycystic ovary syndrome (PCOS). Objective To evaluate the frequency of PCOS in females with resistant acne vulgaris. Patients and methods This case‐controlled study was conducted in the Department of Dermatology and Venereology in The Teaching Hospital in Al‐Najaf during the period from October 2007 to November 2008. One hundred and twenty‐three female patients with resistant acne vulgaris were included in this study. One hundred and twenty‐three women, age‐matched, without acne were enrolled as a control group. Detailed history, clinical examination, abdominal ultrasound study, and hormonal assays were obtained for the patients and the control group. Results One hundred and twenty‐three females with resistant acne were included; their ages ranged from 17 to 40 years with a mean of 25.016 ± 6.041 (SD). One hundred and twenty‐three control women without acne were enrolled; their ages ranged from 17–40 years with a mean of 26.014 ± 6.251 (SD). The patients and the control group are age‐matched (P = 0.192). It was found that 63 patients (51.2%) with resistant acne have PCOS in comparison to only eight control women (6.2%). The difference is highly significant. Conclusion Polycystic ovary syndrome is an important contributing factor in females with resistant acne vulgaris.     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

痤疮丙酸杆菌与痤疮

痤疮丙酸杆菌的结构、分布和生理特点决定其在痤疮发病中的重要作用,尤其与痤疮的炎症损害及严重程度密切有关.目前,针对痤疮丙酸杆菌的痤疮治疗方法众多,包括应用四环素类、克林霉素、红霉素等治疗和过氧苯甲酰或5-氨基酮戊酸光动力疗法等.由于耐药性痤疮丙酸杆菌的出现,抗生素与非抗生素类药物的联合疗法已被证明为最佳治疗手段.痤疮丙酸杆菌全部基因组序列的测定使针对痤疮的菌苗疗法成为可能.     

Polycystic ovary syndrome and acne

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in reproductive aged women. It is typically characterized by hyperandrogenism, chronic anovulation, and polycystic ovaries. Women with PCOS often experience dermatologic manifestations of hyperandrogenism, including hirsutism, acne vulgaris, and androgenic alopecia. This article will review the treatments for acne due to androgen excess in PCOS women.     

Hormonal therapy for acne

Acne affects more than 40 million people, of which more than half are women older than 25 years of age. These women frequently fail traditional therapy and have high relapse rates even after isotretinoin. Recent advances in research have helped to delineate the important role hormones play in the pathogenesis of acne. Androgens such as dihydrotestosterone and testosterone, the adrenal precursor dehydroepiandrosterone sulfate, estrogens, growth hormone, and insulin-like growth factors may all contribute to the development of acne. Hormonal therapy remains an important part of the arsenal of acne treatments available to the clinician. Women dealing with acne, even those without increased serum androgens, may benefit from hormonal treatments. The mainstays of hormonal therapy include oral contraceptives and antiandrogens such as spironolactone, cyproterone acetate, or flutamide. In this article, we discuss the effects of hormones on the pathogenesis of acne, evaluation of women with suspected endocrine abnormalities, and the myriad of treatment options available.