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Acne is a multi-factorial skin disorder of pilosebaceous unit, and environmental exposures play an important role in etiologies of acne, which leads to a group of environmental factors-related acne such as dioxins-induced chloracne, coal tar acne, cigarette smoking, and ultraviolet (UV)-related acne. Generally, these clinical features of environmental factors-induced acne are similar and characterized by non-inflammatory comedones or cysts with less inflammatory lesions, which has big difference from acne vulgaris. The exact mechanism of environmental factors on human skin and acne are still unclear completely. AhR signaling pathway may mediate the action of environmental factors on the pilosebaceous unit, including accelerating terminal differentiation of keratinocytes and switching the differentiation of sebaceous gland cells into keratinocyte-like cells, as well as the reduced lipogenesis of sebaceous glands. Environmental factors-induced acne is quite resistant to conventional therapy and the only effective management is to remove the induced factors. A better understanding and research of how these exogenous factors works and how they contribute to the physiological function of sebocytes, hyperkeratinization, modulation of skin microbiota, initiation of the innate immunity and inflammatory cascade thus leading to the deterioration of acne are needed in the future.

Acne is one of the most common skin inflammatory diseases, representing the top three most prevalent skin conditions in the general population worldwide (Johnson and Roberts, Vital Health Stat 11 (212):i–v, 1–72, 1978; Wolkenstein et al., Arch Dermatol 139(12):1614–9, 2003; Rea et al., Br J Prev Soc Med 30(2):107–14, 1976; Bhate and Williams, Br J Dermatol 168(3):474–85, 2013). The complex physiopathology of this dermatosis involves several key players: sebaceous gland, activation of innate immunity and microbiome with a commensal bacteria Cutibacterium acnes. In this book chapter, we propose to give an overview of the most current findings about acne physiopathology and future medical challenges ahead. This chapter will focus on the commensal bacterium Cutibacterium acnes, as it has a pivotal role in acne physiopathology, its interaction with the different microorganisms constituting skin microbiota and the innate immune system. Based on the scientific literature, this book chapter will also review the innovative therapeutic options that will be developed in the future years.

Skin is the body’s largest organ. It consists of two layers. The outermost layer is the epidermis, which is a stratified squamous epithelium. The second layer is the dermis, comprised of both loose and dense irregular connective tissue. Skin is classified as thick or thin depending on the thickness of the epidermis. Thick skin is found on the palms of the hands and the soles of the feet, whereas skin over the rest of the body is classified as thin. The epidermis is a layered structure with continuous turnover of cells called keratinocytes. Keratinocytes form from stem cells in the basal layer of the epidermis, and then migrate to the surface. As they migrate, they accumulate keratin and eventually undergo apoptosis forming the outermost layer of the epidermis, which sheds the apoptotic cells on a daily basis. In addition to keratinocytes, the epidermis contains melanocytes. These cells produce melanin, which the melanocytes transfer to keratinocytes. Melanin determines the color of skin and provides protection from UV radiation. Skin also contains hair follicles, eccrine sweat glands, apocrine sweat glands, and sebaceous glands, all of which are derived from the epidermis. Skin is richly innervated with free nerve endings and several different types of encapsulated sensory receptors. Common benign neoplasms of the skin are melanocytic nevi (moles), and acrochordons (skin tags).

Knowledge of skin anatomy and function is fundamental for understanding the clinical manifestations and impacts of skin diseases. While true for any organ, this is especially true for the skin, because clinicians can see, touch, and otherwise interrogate the anatomy of this organ directly. Importantly, skin diseases result from deleterious agents or processes that disrupt specific anatomic components of the skin, and induce physiological responses that distort it, to create skin lesions. Recognition of skin lesion significance, and thus diseases, is based upon identifying alterations in normal skin anatomy, including the particular anatomical components that are targeted. Furthermore, the impacts of skin diseases and treatment choices are understood through knowledge of normal skin functions and the consequences of its dysfunction. This chapter reviews basic aspects of feline skin structure and function, with citations from the literature where available, and draws heavily on the comparative information available for humans and dogs.

The natural hairstyle mirrors in various contexts self-expression; in particular, it expresses female beauty. The types of hair care and styles available, as well as the side effects of the techniques employed, are often poorly taken into account. The nail and skin glands are also here briefly considered.

Daniel Turner (1667–1741) of London was the first to emphasize dietary restrictions for acne therapy. Joseph Jakob Plenck (1735–1807) of Vienna related the frequency of acne in young people to a rich diet. Since then acne and diet has been a continuing debating issue. Over the last five decades, diet has been declined to play a role in acne pathogenesis. In 1969, the study of Fulton and coworkers, which was not controlled by glycemic index, showed that high amounts of chocolate did not affect the course of acne vulgaris or the output or composition of sebum. Though much more critical work is required, present knowledge suggests that the sebaceous gland has a high degree of autonomy. In 2002, Cordain and coworkers observed completely acne-free adolescents of Kitava islanders living under Paleolithic nutritional conditions excluding hyperglycemic carbohydrates, milk and dairy products. Further observations of low acne prevalence rates in less developed Paleolithic populations such as the Arche hunters in Paraguay, natives in rural Brazil, Eskimos, Okinawa islanders, and Chinese consuming traditional Chinese food suggested that acne is a disease of Western civilization.

Fibroadenoma is a benign tumor of the mammary gland, which belongs to a group of mixed connective tissue and epithelial tumors. It constitutes up to 95% of all benign breast masses. Phyllodes tumor (phyllodes fibroadenoma, intracanalicular fibroadenoma with a cell stroma) is a mixed connective tissue and epithelial tumor. It demonstrates the incidence not exceeding 0.5–2% of all breast lesions and 2.5–5.4% of all fibroadenomas. Juvenile (giant, cellular) fibroadenoma is a benign fibroepithelial tumor with enlarged convoluted ducts, usually with papillary-cribose proliferation of the epithelium and stroma, with edema and/or desmoplasia. Lipoma is a benign tumor originating from adipose tissue. It accounts for 9% of all breast lesions. True lipoma consists of mature adipose tissue surrounded with a capsule. Intraductal papilloma is represented with a lesion that grows within the lumen of lactiferous ducts. Solitary or multiple lesions may arise. Intraductal papilloma is associated with abnormal discharge from the nipples. Atheroma is retention cyst of the sebaceous gland located in the benign skin and subdermal tissues, which occurs by increased sweating of the sebaceous gland, occlusion of its duct, and forming of a capsule around the fatty content.

Activation of the immune system is a central event in the development of acne, and our understanding of this process is rapidly expanding. In this chapter, we describe how P. acnes, sebaceous glands, and keratinocytes contribute to inflammation in acne and how current acne treatments modulate this immune response. Specifically, we address the role of anti-microbial peptides, Toll-Like Receptors (TLRs), sebaceous lipids as well as cytokines and the role of the inflammasome as driving inflammation in acne. The anti-inflammatory activities of retinoids, tetracyclines and other therapies are discussed.

The etiology of hidradenitis suppurativa (HS) is not fully described, in spite of the considerable morbidity associated with the disease. Patients with HS are often under the care of many different specialties such as general practice, dermatology or surgery due to its previous status as an orphan disease. Epidemiologically HS is associated with positive family history, female sex, smoking and increased body mass index (BMI), and clinically the presence of bacteria and altered immune responses have been suggested as possible etiologies [1, 2].

A 26-year-old male presented to Primary Care with an asymptomatic papular rash in the supraclavicular area. The patient was initially treated with a topical corticosteroid, followed by a topical antifungal, and had no response to either. The papular rash was later evaluated by Dermatology and diagnosed as juxtaclavicular beaded lines (JCBL), a rare, benign sebaceous gland hyperplasia. The condition is more predominant among African Americans, and is associated with the onset of puberty, and long-term corticosteroid use. The papules of JCBL are typically 1–2 mm, flesh-colored or yellow in color, and arranged in a line adjacent to the clavicles. They are sometimes pierced by a fine hair. Due to their benign nature, JCBL papules do not require treatment. If they are cosmetically bothersome, topical retinoid cream, electrodesiccation, and CO2 lasers can reduce their appearance; however, treatment cannot guard against recurrence.

The primary neoplasms of the skin are discussed in this chapter. Skin metastases originating from internal malignancies are not included in this wide group of neoplasia, as they will be briefly covered in the Chap. 5. With rare exceptions, such as ulcerative feline squamous cell carcinoma and exfoliative erythematous dermatitis in some cases of canine epitheliotropic lymphoma, almost all skin neoplasia are nodules or plaques. For this reason, an approach based on clinical signs, as used for inflammatory skin diseases, is not possible. Therefore, to discuss the cytology of skin neoplasms, a classification based on the cytological and histological morphology of the neoplastic cells must be used.

In this chapter, the morphology of the cells that make the skin is discussed. To better interpret the cytological specimens collected from skin lesions, it is mandatory to know the morphology of the cells that compose the epidermis, the dermis and the subcutaneous tissue, in addition to the cells that normally reside in the dermis and finally, those produced from bone marrow that reach the skin via the bloodstream during inflammatory processes.

Hair follicles contain nestin-expressing pluripotent stem cells which originate above the bulge area of the follicle, below the sebaceous gland. We have termed these cells hair follicle-associated pluripotent (HAP) stem cells. We have established efficient cryopreservation methods of the hair follicle that maintain the pluripotency of HAP stem cells as well as hair growth. We cryopreserved the whole hair follicle by slow-rate cooling in TC-Protector medium or in DMSO-containing medium and storage in liquid nitrogen or at −80 °C. After thawing and culture of the cryopreserved whisker follicles, growing HAP stem cells formed hair spheres. The hair spheres contained cells that differentiated to neurons, glial cells, and other cell types. The hair spheres derived from slow-cooling cryopreserved hair follicles were as pluripotent as hair spheres from fresh hair follicles. We have also previously demonstrated that cryopreserved mouse whisker hair follicles maintain their hair-growth potential. DMSO better cryopreserved mouse whisker follicles compared to glycerol. DMSO-cryopreserved hair follicles also maintained the HAP stem cells, evidenced by P75ntr expression. Subcutaneous transplantation of DMSO-cryopreserved hair follicles in nude mice resulted in extensive hair fiber growth over 8 weeks, indicating the functional recovery of hair-shaft growth of cryopreserved hair follicles. HAP stem cells can be used for nerve and spinal-cord repair. This biobanking of hair follicles can allow each patient the potential for their own stem cell use for regenerative medicine or hair transplantation.

The sebaceous gland (SG) is an acinous holocrine-secreting appendage of the epidermis serving many important functions of the skin. Its continuous cellular renewal and sebum production by mature sebocytes requires replenishment by undifferentiated cells of the periphery of the gland. Over the last years, the contribution of different stem and progenitor cell populations of the hair follicle (HF) structure to SG regeneration and SG disease processes has been investigated. For the near future it remains to decipher the underlying mechanisms of SG cell fate determination as well as the role of abnormal stem cell (SC) regulation for severe skin diseases, including defective proliferation and differentiation of the SG, abnormal barrier and lipid metabolism, as well as development of sebaceous tumors. Here we discuss our current thinking and fundamental recent findings on the diverse repertoire of epidermal SC functions in development, regeneration and pathophysiology of the SG.

• Rudimentary mammary glands isolated or associated with sebaceous gland (as in Montgomery’s glands) may be (rarely) found just below the areola. This condition should be taken into consideration, just like mammary glands (more rarely) found deeper, beyond the pectoral fascia. • The skin of the areola and the nipple, for its contents of subcutaneous glands, is more prone to different kinds of dermatological diseases. True dermatitis is generally bilateral and part of other localisations anywhere in the body. • Paget’s disease should be taken in consideration in all cases of unilateral eczema of the areola. • Aside from the well-known and indolent dermatitis, radiation therapy may promote some dermatological diseases as herpes zoster and morphea. • For unexplained clinical observations, factitial diseases should be considered for patient with emotional and psychotic problems, who have a history of seeking frequent medical attention.