Infundibular Hyperkeratosis Research Articles

New Treatments for Acne in The Context of Antibiotic Resistance

Acne has long been recognized as a widespread skin condition, and its prevalence is currently increasing. One of the top 10 epidemics in the world right now, it has a serious psychological toll on its victims. Four interconnected processes, including inflammation, increased sebum production, follicular infundibular hyperkeratosis, and Chlamydia acne growth, make up the disease's complicated pathophysiology. Antibiotics that target P. acnes have been a successful and popular way to treat acne for the past 40 years, even though the pathophysiology of acne is not entirely understood. The emergence of antibiotic resistance, however, is a persistent issue with a variety of negative consequences. Isotretinoin and antiandrogen therapy are frequent therapies for certain of them. This article summarizes the effectiveness and safety of oral antibiotics for acne treatment in recent years as well as some other recent treatment research, operating under the premise that the current domestic and international clinical trials of acne vulgaris are insufficient. The goal is to raise awareness of acne vulgaris.

A new diagnostic paradigm for Erythromelanosis Follicularis Faciei et Colli: Dermoscopic and reflectance confocal microscopic features

Introduction: Erythromelanosis Follicularis Faciei et Colli is a rare variant of Kerastosis pilaris, characterized by a clinical triad of erythema, hyperpigmentation and follicular papules involving bilaterally cheeks, preauricular and maxillary areas of young male or, more rarely, female patients Case presentation: A 21-year-old Caucasian woman presented symmetrical patches of hyperpigmentation, erythema with microscopic telangiectasias and tiny follicular papules involving cheeks, preauricular and maxillary areas, forehead, pinna and neck since childhood. Lesions were asymptomatic but caused profound cosmetic disfigurement and had a negative impact on her social life. The patient underwent a non-invasive diagnostic procedure with epiluminescence and confocal microscopy. Dermoscopic examination revealed prominent yellowwhitish follicular keratotic plugging over a reddish background with short fine telangiectasia in the perifollicular and interfollicular areas. Furthermore, RCM features displayed the presence of enlarged the presence of enlarged follicular openings, absence of demodex mites within the follicles and slight infundibular hyperkeratosis. At the level of the epidermal-dermal junction hyperpigmentation of the epithelial basal cell layer and dilation of dermal capillaries inside dermal papillae were observed, correlating to typical histological features of EFFC. Our patient benefited from the topical use of tretinoin 0.05% cream, with attenuation of the instrumental pictures. Conclusion: Characteristic plugging over a reddish background and morphological features revealed by RCM may be helpful for assessment and monitoring in patients with EFFC. Starting from the observation of this case we would like to underline the importance of a noninvasive diagnostic procedure and an effective therapy for such a rare condition. Keywords: Erythromelanosis Follicularis Faciei et Colli; Erythromelanosis Follicularis Faciei diagnosis; Dermoscopy; In vivo reflectance confocal microscopy.

Aetiology and pathogenesis of hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disorder. Patients develop inflamed nodules and abscesses and, at later stages of disease, epithelialized tunnels and scars in skinfolds of axillary, inguinal, gluteal and perianal areas. Quality of life is affected due to severe pain, purulent secretion, restricted mobility and systemic involvement. Genetics and lifestyle factors including smoking and obesity contribute to the development of HS. These factors lead to microbiome alteration, subclinical inflammation around the terminal hair follicles, and infundibular hyperkeratosis, resulting in plugging and rupture of the follicles. Cell-damage-associated molecules and propagating bacteria trigger inflammation and lead to massive immune cell infiltration that clinically manifests as inflamed nodules and abscesses. The immune system plays a key role also in the progression and chronification of skin alterations. Innate proinflammatory cytokines (e.g. interleukin-1β and tumour necrosis factor-α), mediators of activated T helper (Th)1 and Th17 cells (e.g. interleukin-17 and interferon-γ), and effector mechanisms of neutrophilic granulocytes, macrophages and plasma cells are involved. Simultaneously, skin lesions contain anti-inflammatory mediators (e.g. interleukin-10) and show limited activity of Th22 and regulatory T cells. The inflammatory vicious circle finally results in pain, purulence, tissue destruction and scarring. Chronic inflammation in patients with HS is also frequently detected in organs other than the skin, as indicated by their comorbidities. All these aspects represent a challenge for the development of therapeutic approaches, which are urgently needed for this debilitating disease. This scholarly review focuses on the causes and pathogenetic mechanisms of HS and the potential therapeutic value of this knowledge.

Transverse sectioning in the evaluation of skin biopsy specimens from alopecic dogs.

Transverse sectioning of skin biopsy specimens has revolutionised assessment of human alopecia by demonstration of every hair in each specimen, allowing quantitative evaluation of follicular activity. Since only vertical sectioning is performed routinely in veterinary laboratories, we aimed to determine whether transverse sectioning was a valuable technique in assessment of canine alopecia. Paired vertical and transverse sections of biopsy specimens from 31 alopecic dogs were examined independently in triplicate in random order and blinded to previous diagnosis using a standard check-list proforma. Assessments of key features (follicular activity [anagen/telogen], infundibular hyperkeratosis, sebaceous gland abnormalities, pigment clumping, dermal inflammation) by each sectioning method were compared. In the 31 cases, (atrophic [n=13], dysplastic [n=12], inflammatory diseases [n=6]), follicular inactivity scores (median, [lower-upper quartile]) in transverse sections significantly exceeded those in vertical sections (transverse 4 [3-5], vertical 3 [2-4]). Agreement between the two sectioning planes was moderate for infundibular hyperkeratosis (kappa=0.5210) and dermal inflammation (0.4351), fair for sebaceous gland abnormalities (0.3966) and pigment clumping (0.2197), but slight for follicular activity (0.1041). Vertical sectioning demonstrated diagnostically important epidermal pathology (n=2) and dermal thinning (n=3) whereas transverse sectioning enhanced assessment of hair growth phase (n=11), follicular structure and architecture (n=11), and focal luminal or mural folliculitides (n=3). Transverse sectioning confers significant benefits and complements traditional vertical sectioning in the histological assessment of canine hair follicle diseases, particularly when subtle abnormalities comprise distorted compound follicle architecture, hair cycle arrest or when relatively few adnexal structures are affected.

Clinical and pathological features of hair coat abnormalities in curly coated retrievers from UK and Sweden.

To gain information on hair loss amongst curly coated retrievers by questionnaire and to define the clinical and pathological features of hair coat abnormalities in affected dogs in the United Kingdom and Sweden. Questionnaires were completed by members of the Curly Coated Retriever Clubs. Fourteen dogs (six in the United Kingdom, eight in Sweden) were clinically examined and skin/hair samples collected for microscopy and histopathology. Blood was collected for haematological, biochemical and endocrine assays. Of 90 dogs surveyed, 39 had current or previous episodes of symmetrical, non-pruritic alopecia and or frizzy coat changes, usually affecting caudal thighs, axillae, dorsum and neck before 18 months of age; 23 dogs had a waxing/waning course. Examined dogs generally matched the pattern described in questionnaires. Hair shaft anomalies comprised occasional distorted anagen bulbs (10 dogs) and transverse fractures (8 dogs). Vertical histopathological sections showed infundibular hyperkeratosis (28 of 30 sections) and low-grade pigment clumping (17 of 30). Subtle telogenisation of hair follicles was unequivocally confirmed by transverse histomorphometric analyses. The follicular dysplasia of curly coated retriever reported here is similar to that of Irish water spaniels and Chesapeake Bay retrievers but distinct from that of Portuguese water dogs. The genetic basis requires further assessment.

Deciphering the microbiology of hidradenitis suppurativa: a step forward towards understanding an enigmatic inflammatory skin disease.

Keywords: anaerobes; hidradenitis suppurativa; inflammatory disease; microbiology; soft tissue and skin infections

Acne inversa: difficulties in diagnostics and therapy.

Acne inversa (hidradenitis suppurativa) is a potentially severe and chronic inflammatory disease with a significant negative influence on the quality of life. Usually, lesions are located in the areas of skin folds and it is characterized by the presence of painful nodules and fistulas with a tendency to tissue fibrosis. Currently, it is suggested that follicular occlusion by infundibular hyperkeratosis plays a crucial role in pathogenesis and an occupation of apocrine sweat glands is a secondary phenomenon. Most often, it refers to men after puberty. This article tries to present the latest theory concerning the etiology of inverted acne and methods of its treatment. It also describes the most common errors in diagnostic and therapeutic procedures, which are mainly connected with repeated and long antibiotic therapy and not radical surgical treatment.

Histological and dermatoscopic description of sphynx cat skin.

Histological and hair coat abnormalities of the alopecic sphynx cat have not been described in detail. The hairless allele (hr) in sphynx cats represents a mutation in the gene for keratin71, a protein expressed in the inner root sheath of humans and mice. To describe the histological and dermatoscopic abnormalities of sphynx cat skin. Skin biopsies were collected from 14 sphynx cats and five cats with normal coats. Dermatoscopic examinations were performed on 11 sphynx cats and six additional control cats. Vertical and horizontal sections of skin biopsy samples from sphynx and control cats were reviewed. Dermatoscopic images were compared between sphynx and control cats. Sphynx cat hair follicles were often small, curved and kinked and demonstrated infundibular hyperkeratosis and dilatation. Changes in the inner root sheath of sphynx cats included a poorly defined Henle's layer in addition to vacuolar-like changes and eosinophilic globules in Huxley's layer. Dermal papillae in sphynx cat anagen bulbs lacked the normal flame shape and were surrounded by epithelial cells arranged in a disorderly manner. The degree of follicular abnormalities varied between follicles. Follicular density was similar for both sphynx cats and control animals. Sphynx cat hair shafts were misshapen, smaller in diameter and rarely medullated. Dermatoscopy revealed similar hair coat density in sphynx and control cats. Sphynx cats demonstrated hair follicle dysplasia, with abnormal shaft production but without a decrease in follicle quantity. Abnormalities in sphynx cat follicles are similar to those in murine KRT71 mutants and suggest abnormal hair shaft keratinization.

Activation of Nrf2 in keratinocytes causes chloracne (MADISH)‐like skin disease in mice

The transcription factor Nrf2 is a key regulator of the cellular stress response, and pharmacological Nrf2 activation is a promising strategy for skin protection and cancer prevention. We show here that prolonged Nrf2 activation in keratinocytes causes sebaceous gland enlargement and seborrhea in mice due to upregulation of the growth factor epigen, which we identified as a novel Nrf2 target. This was accompanied by thickening and hyperkeratosis of hair follicle infundibula. These abnormalities caused dilatation of infundibula, hair loss, and cyst development upon aging. Upregulation of epigen, secretory leukocyte peptidase inhibitor (Slpi), and small proline-rich protein 2d (Sprr2d) in hair follicles was identified as the likely cause of infundibular acanthosis, hyperkeratosis, and cyst formation. These alterations were highly reminiscent to the phenotype of chloracne/“metabolizing acquired dioxin-induced skin hamartomas” (MADISH) patients. Indeed, SLPI, SPRR2, and epigen were strongly expressed in cysts of MADISH patients and upregulated by dioxin in human keratinocytes in an NRF2-dependent manner. These results identify novel Nrf2 activities in the pilosebaceous unit and point to a role of NRF2 in MADISH pathogenesis.

Epidemiology of Hidradenitis Suppurativa: Prevalence, Pathogenesis, and Factors Associated with the Development of HS

Hidradenitis suppurativa is a common skin disease with an estimated prevalence of approximately 1 %. The disease is characterized by painful nodules localized mainly in the inverse body areas, such as the axillae and groin. The pathogenesis of HS is still not fully understood, but infundibular hyperkeratosis, causing follicular occlusion, is thought to be the primary event followed by rupture with an inflammatory response. Multiple factors are associated with HS, especially smoking and obesity. More recently, the genetic background and an aberrant innate immune response have gained more attention as predisposing factors. In this review, we discuss the prevalence, pathogenesis, and relevant factors influencing the development of HS.

Acne inversa (Hidradenitis suppurativa): A review with a focus on pathogenesis and treatment

Acne inversa (AI) is a disabilitating chronic inflammatory disease with major negative impact on quality of life and significant co-morbidities. This is an important link to insights into immune dysfunction, which stimulated therapeutic approaches like tumor necrosis-α inhibitor therapy. This new off-label drug treatment is particularly beneficial when used in combination with wide excision of inflamed skin and subcutaneous tissue. Retinoids have been reported to be helpful in secondary prevention. The standard of therapy in advanced cases is surgery with wide excisions and healing by secondary intention. This treatment results in significant reduction of complaints and achieves satisfactory body contouring.

Hidradenitis suppurativa: a review of cause and treatment

Hidradenitis suppurativa is a chronic or relapsing inflammatory cutaneous disorder manifested by recurrent formation of abscesses, fistulating sinus and scarring in the apocrine-gland-bearing skin. This review discusses the different aetiological theories and management opportunities. Current understanding of the pathogenesis suggests that hyperkeratosis of the infundibulum, leading to follicular occlusion of the pilosebaceous unit plays a role. Bacterial infection with staphylococci, Escherichia coli and streptococcus is considered as a secondary event in the pathogenesis. Smoking and obesity are both known as risk factors and are associated with more severe disease course. Recently, more attention has been put into the understanding of the immunopathology of the skin and the results indicate that hidradenitis suppurativa may be considered as an inflammatory disease of unknown cause based on a defect in the hair follicle immunity. The treatments are most appropriately chosen on the basis of disease severity and the existence of any associated risk factors or comorbidities. There are three levels in the management of hidradenitis suppurativa: topical options, systemic options and surgical methods including laser therapy. At each level several treatment principles have shown themselves to be efficient, and may therefore be used either alone or in combination. Therapies are generally effective against microorganisms, inflammation or infundibular hyperkeratosis. Where an antimicrobial therapy is used, the drugs used often have significant additional immunomodulatory effects. The recent studies give us a better insight into the pathogenesis of hidradenitis suppurativa and should translate into improved therapies.

Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae

Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles.

The potential role of acetylcholine receptors in acne inversa (HS) pathogenesis

Acne inversa is a chronic inflammatory disorder that has been shown to be influenced by tobacco smoking, which may represent a ‘natural’ model of exogenous nicotine‐mediated activation of the nicotinic acetylcholine receptors (AChR). In previous works, we have provided a concise mapping of AChR present in normal skin and have demonstrated a crucial role of AChR in terminal differentiation and barrier formation. In addition, several studies suggest a role for the non‐neuronal cholinergic system in immunomodulation. To date, the AChR composition of the cells involved in the pathogenesis of acne inversa has not yet been characterized.Using immunohistochemistry and RT – PCR, we could show that nicotinic α3, α5, α7 and α9 AChR as well as muscarinic M1–M5 AChR are produced in lesional epidermis in a pattern comparable with normal epidermis. In vitro and in lesional skin, we could demonstrate the presence of α3, α5 and α7 nAChR as well as M1–M5 mAChR in variable amounts on macrophages. In lesional epidermis, the choline‐acetyltransferase (ChAT)‐reactivity was particularly pronounced in the epidermal basal layer, while in the sinus tracts, ChAT reactivity was extended to all epithelial layers. High levels of ChAT especially in the hair follicle infundibulum indicate that endogenously produced ACh may act synergistically with tobacco‐delivered nicotine in aggravating infundibular hyperkeratosis. ChAT could not be detected in macrophages in vitro or in vivo indicating that macrophages do not actively contribute to ACh signalling in acne inversa but may rather be targets of ACh, and hence nicotine induced immunomodulation.

Generalized alopecic and cystic dermatosis in a cat: a counterpart to the hairless mouse phenotype or a unique congenital dermatosis?

A 2-year-old, male neutered, domestic semi-long-haired cat was presented with a 1.5-year history of progressive, initially nonpruritic alopecia and malodorous greasy exudate affecting the distal extremities, trunk and neck but sparing the head and tail. The extensive alopecia and 'seborrhoea' were associated with severe thickening of the skin and fold formation on the dorsal head and distal extremities as well as the lateral thorax and abdomen. The hair was easily epilated, numerous milia were seen on the ventral abdomen and the caudal and lateral thighs, and mild paronychia was present. Histopathological examination of skin biopsies revealed marked cystic dilation of hair follicles and sebaceous glands with follicular hypoplasia, infundibular hyperkeratosis and variable associated inflammation. Systemic glucocorticoid therapy in combination with topical washes with chlorhexidine and miconazole resulted in a marked improvement and some hair regrowth, but the cat was subsequently lost to follow-up. The dermatosis resembles a number of conditions in other species, but it is not clear whether it is a counterpart to the hairless mutant mouse or is a unique dermatosis.

FC‐11 Histopathology of alopecia X

Dogs with endocrinopathy have been reported to have hair follicles with excessive trichilemmal keratinization (flame follicles). These follicles have been described in cases clinically diagnosed as hypothyroidism, hyperadrenocorticism, hyposomatotropism and sex hormone abnormality. Breed variation in the incidence of these follicles has also been described. Recently, endocrine alopecias have been better defined, and a number of these conditions (previously known as congenital adrenal hyperplasia, pseudo‐Cushing's disease, castration‐responsive dermatosis and adult‐onset hyposomatotropism) are now grouped under the name alopecia X. In this prospective study, a group of 24 spitz‐type dogs, which included 15 Pomeranians, had an extensive hormonal work‐up. This included thyroid and adrenocorticotrophic hormone stimulation tests and sex hormone assays. Histopathology of the skin specimens collected from alopecic and clinically normal skin indicated features common to many endocrinopathies such as surface and infundibular hyperkeratosis and comedone formation. However, catagenization with flame follicle formation was a prominent feature of skin specimens from 22 dogs. This feature was so marked in 20 of these specimens that it was considered to be diagnostic for alopecia X when the specimens were evaluated in a blinded manner. The other two specimens could not be differentiated reliably from hyperadrenocorticism. Histopathology is a useful diagnostic procedure to support a diagnosis of alopecia X in dogs. Funding: Self‐funded.

FC‐10 Adult‐onset hair loss in Chesapeake Bay retrievers: a clinical and histological study

Hair loss in Chesapeake Bay retrievers has been increasingly recognized by breeders in recent years. Anecdotal reports suggest an endocrine disorder or follicular dysplasia as the underlying cause, but no scientific study has been done to investigate the underlying problem. A prospective study was carried out in collaboration with the American Chesapeake Club. Affected dogs were recruited into the study. Routine dermatological and hormonal (blood and urine) tests, and skin biopsies were performed. Ten dogs (age 1.5–10 years), seven females (two spayed) and three males (two neutered), were included in the study. All dogs had mild or severe hair loss affecting the lateral ventral chest, flanks, rump and thighs. Affected dogs were clinically healthy. Hormonal tests revealed normal thyroid hormone panels, insulin‐like growth factor‐1 levels, and urinary cortisol:creatinine ratios in samples collected for ten consecutive days. In six of 10 dogs, an adrenal hormone panel showed slight or moderate increased values pre‐ and/or post‐ACTH stimulation of cortisol (three of six), 17‐hydroxyprogesterone (five of six), androstenedione (three of six), estradiol (two of six) and progesterone (six of six). The major histopathologic changes resembled canine flank alopecia and follicular dysplasia with pronounced infundibular hyperkeratosis, mild follicular atrophy, and occasional melanin clumping with dystrophic hair shafts. Chesapeake Bay retrievers suffer from a type of hair loss that is likely related to an abnormal production of adrenal sex hormone. Further studies are currently underway to determine if there is a heritable basis for this disease and to evaluate therapeutic options. Funding: University of Pennsylvania.

Follicular and perforating disorders.

Pathologic changes associated with hair follicles include infundibular hyperkeratosis, inflammation, mucinous degeneration and transepidermal elimination of foreign material. Because of the focal nature of the pathologic changes multiple sections are often useful in establishing the correct diagnosis.