What's new in the physiopathology of acne?

There are four central factors that contribute to acne physiopathology: the inflammatory response, colonization with Propionibacterium acnes, increased sebum production and hypercornification of the pilosebaceous duct. In addition, research in the areas of diet and nutrition, genetics and oxidative stress is also yielding some interesting insights into the development of acne. In this paper we review some of the most recent research and novel concepts revealed in this work, which has been published by researchers from diverse academic disciplines including dermatology, immunology, microbiology and endocrinology. We discuss the implications of their findings (particularly in terms of opportunities to develop new therapies), highlight interrelationships between these novel factors that could contribute to the pathology of acne, and indicate where gaps in our understanding still exist.

Basal cell carcinoma arising in a nevus sebaceus in a child with facial trichoepitheliomas.

Nevus sebaceus (NS) is a congenital skin hamartoma that presents in childhood. Tumors may arise within these lesions over time. Mutations in the PTCH gene have been associated with both NS and some of the developing tumors. Only nine documented cases of basal cell carcinoma arising in nevus sebaceus in childhood are available. We present a case of an 8-year-old male with nevus sebaceus who developed a basal cell carcinoma. Evaluation for constitutional PTCH gene mutation and loss of heterozygosity (LOH) from the BCC within the NS did not reveal an underlying mutation. We further discuss the literature regarding prophylactic excision of NS.

Severe ulcerative and granulomatous pinnal lesions with granulomatous sebaceous adenitis in unrelated vizslas.

Granulomatous sebaceous adenitis (GSA) is uncommon in dogs; however, certain breed predilections exist. In this report, three cases of GSA in unrelated vizslas have been described. All cases initially presented with episodes of otitis externa followed by severe inner pinnal lesions. In one case, multifocal coalescing inner pinnal ulceration appeared 4 wk prior to the occurrence of the skin lesions. The other two cases presented with simultaneous pinnal and skin lesions following episodes of bilateral otitis. The pinnae were diffusely erythematous and had multiple coalescing erosions and ulcers. The body lesions consisted of multifocal alopecia, papules, and fine scales. Biopsies of the skin and pinnae confirmed GSA. Two dogs responded to treatment with synthetic retinoids and cyclosporin A, respectively. One dog was not treated, and the owners preferred euthanasia when the ear lesions recurred and did not respond to glucocorticoids. To the best of the authors' knowledge, GSA with multifocal coalescing ulcerative pinnal lesions has not previously been reported.

An odd looking lesion.

Mark, 54 years of age, has a nontender lump on his praecordium that has been present 'for a long time'. He vaguely recalls a smaller lump at the same site years ago, which he squeezed, with subsequent resolution. Mark denies any bleeding, however, he has noticed occasional yellowish-brown stains on his shirt.

Coexistence of basal cell carcinomas and multiple sebaceous gland hyperplasias in a cyclosporine (ciclosporin)-treated renal transplant recipient.

A 55-year-old man presented with multiple, asymptomatic, yellowish papules on his face with a 4-year history, and two non-healing tumoral lesions on his nose with a 7-month history. He was a renal transplant recipient and had been treated with cyclosporine (ciclosporin) for 9 years. A biopsy from the asymptomatic, yellowish papule on the face showed sebaceous gland hyperplasia, and biopsies from the lesions on the nose revealed basal cell carcinomas. The lesions on the nose were excised. Sebaceous gland hyperplasia and skin cancers are among the cutaneous neoplasms observed in renal transplant recipients receiving cyclosporine. To our knowledge, this is the third reported case of the coexistence of basal cell carcinomas and multiple sebaceous gland hyperplasias in a cyclosporine-treated renal transplant recipient.

Multiple clustered dermatofibroma with overlying sebaceous hyperplasia.

Multiple clustered dermatofibroma is a very rare clinical variant of the dermatofibroma, and sebaceous differentiation overlying dermatofibromas is also unusual. We report the first case of a multiple clustered dermatofibroma with overlying sebaceous hyperplasia.

Is acne an infection of blocked pilosebaceous follicles? Implications for antimicrobial treatment.

A model is proposed which is based on the assumption that acne is due to infection of functionally blocked pilosebaceous follicles by propionibacteria. Noninflamed lesions, which are first visible during the adrenarche in acne-prone individuals, do not contain propionibacteria. Comedogenesis appears to be independent of bacterial infection and may be driven by high levels of bioactive interleukin-1 alpha derived from ductal hyperkeratinocytes. The stimulus which triggers interleukin-1 alpha production is unknown. Formalin killed Propionibacterium acnes failed to stimulate production of the cytokine by cultured human keratinocytes in vitro. Inflamed lesions are thought to arise from microcomedones, but the initiating events are unknown. Evidence that propionibacteria are involved in the generation of inflammatory lesions is inconclusive. The cellular infiltrate is consistent with a type IV hypersensitivity response to one or more persistent lesional antigens, not necessarily bacterial. The potent adjuvant activity of P. acnes would up-regulate the immune response to any antigen which came into contact with the mononuclear cell infiltrate. Antibiotics are widely used in the treatment of acne, and their effects in selecting a predominantly resistant commensal population are well recognized. Although they reduce numbers of propionibacteria on the skin, other modes of action may contribute to or explain their therapeutic efficacy. At a time when there is global concern that antibiotic resistance rates in common bacterial pathogens may threaten our future ability to control bacterial infections, practices which promote the spread of antibiotic-resistant bacteria must be fully justified. A thorough reappraisal of the role of propionibacteria in acne is overdue. It is likely that further experimental work is needed to confirm or refute that P. acnes is aptly named.

Appraisal of transverse nasal groove: a study.

BACKGROUND: Transverse nasal groove is a condition of cosmetic concern which awaits due recognition and has been widely described as a shallow groove that extends transversely over the dorsum of nose. However, we observed variations in the clinical presentations of this entity, hitherto undescribed in literature. AIMS: We conducted a clinicoepidemiological study of transverse nasal lesions in patients attending our outpatient department. METHODS: We conducted a prospective observational study. We screened all patients attending our out-patient department for presence of transverse nasal lesions, signs of any dermatosis and associated other skin conditions. RESULTS: One hundred patients were recruited in the study. Females (80%) predominated over males. Most patients were of 15-45 years age group (70%). Majority of the transverse nasal lesions were classical transverse nasal groove (39%) and others included transverse nasal line (28%), strip (28%), ridge (4%) and loop (1%). Seborrhoeic diathesis was the most common condition associated with transverse nasal lesion. CONCLUSIONS: Occurrence of transverse nasal line, strip, ridge and loop, in addition to classical transverse nasal groove implies that latter is actually a subset of transverse nasal lesions. Common association of this entity with seborrheic dermatitis, seborrhea and dandruff raises a possibility of whether transverse nasal lesion is a manifestation of seborrheic diathesis.

An unusual hamartoma of the folliculosebaceous-apocrine unit: a case report.

Hamartoma is a neoplasm-like lesion composed of an abnormal mixture of tissues native to the area. We report on an unusual example of a hamartomatous lesion that showed an abnormal mixture of elements of the folliculosebaceous-apocrine unit and arrector pili muscle. A 13-year-old female presented with two nodules situated 2 cm apart on the lower leg that were present since birth. The patient reported some enlargement and slight pain of the otherwise asymptomatic lesions during 2 years, before they were surgically removed. The patient obviously had no skin problems afterwards; her 12-year follow-up was significant for leucopenia and nephrolithiasis. The biopsies from both lesions looked identical. Each lesion was biphasic, i.e. composed of a predominant mesenchymal component and epithelial elements. The mesenchymal part resembled a leiomyoma, or in minor areas, the constituting cells had a myofibroblastic appearance. Encased within the mesenchymal component were large infundibulocystic structures and plentiful grouped and scattered roundish solid epithelial nodules, duct-like, glandular, and tubular elements. Some of the epithelial structures were reminiscent of those seen in tubular apocrine adenoma; others resembled syringomatous elements. We interpreted this unusual lesion as a hamartoma of the folliculosebaceous-apocrine unit.

Zileuton, an oral 5-lipoxygenase inhibitor, directly reduces sebum production.

BACKGROUND: Zileuton, a 5-lipoxygenase inhibitor, reduces the number of inflammatory lesions in moderate acne and inhibits the synthesis of sebaceous lipids. OBJECTIVE: To detect whether zileuton directly reduces sebum synthesis. METHODS: A 40-year-old female with mild disseminated sebaceous gland hyperplasia and seborrhea was treated with zileuton 4 x 600 mg/day over 2 weeks, was followed-up for 6 weeks after discontinuation of zileuton and was re-treated with low-dose isotretinoin 10 mg/2nd day over 5 weeks. Casual skin surface lipids and sebum synthesis were determined. RESULTS: Under treatment with zileuton increased casual skin surface lipids were normalized and synthesis of facial sebum was decreased. Six weeks after discontinuation of treatment casual skin surface lipids were increased again and synthesis of sebum returned to baseline. Subsequent low-dose isotretinoin treatment led to similar changes of casual skin surface lipids and sebum synthesis with zileuton already after 2 weeks. CONCLUSION: Zileuton directly inhibits sebum synthesis in a transient manner with a potency similar to low-dose isotretinoin at least in our patient.

Should nevus sebaceus of Jadassohn in children be excised? A study of 757 cases, and literature review.

The incidence of basal cell carcinoma and the need for prophylactic excision in children with nevus sebaceus of Jadassohn have been a topic of controversy. The authors performed a retrospective analysis of 757 cases from 1996 to 2002 in children aged 16 years or younger. No cases of basal cell cancer were found in the nevus sebaceus group. Recent studies in children corroborate these findings and question the need for prophylactic surgical removal of the nevus sebaceus.