Homeostatic Control of Sebaceous Glands by Innate Lymphoid Cells Regulates Commensal Bacteria Equilibrium.

Immune cells and epithelium form sophisticated barrier systems in symbiotic relationships with microbiota. Evidence suggests that immune cells can sense microbes through intact barriers, but regulation of microbial commensalism remain largely unexplored. Here, we uncovered spatial compartmentalization of skin-resident innate lymphoid cells (ILCs) and modulation of sebaceous glands by a subset of RORγt+ ILCs residing within hair follicles in close proximity to sebaceous glands. Their persistence in skin required IL-7 and thymic stromal lymphopoietin, and localization was dependent on the chemokine receptor CCR6. ILC subsets expressed TNF receptor ligands, which limited sebocyte growth by repressing Notch signaling pathway. Consequently, loss of ILCs resulted in sebaceous hyperplasia with increased production of antimicrobial lipids and restricted commensalism of Gram-positive bacterial communities. Thus, epithelia-derived signals maintain skin-resident ILCs that regulate microbial commensalism through sebaceous gland-mediated tuning of the barrier surface, highlighting an immune-epithelia circuitry that facilitates host-microbe symbiosis.

Microbial colonization of normal skin: Direct visualization of 194 skin biopsies.

Recent genetic studies have suggested the presence of numerous microbial species on and in the skin. We characterised microbial colonization of a large collection of skin biopsies from 194 healthy subjects by fluorescence assay. Forty per cent of all biopsies did not show any evidence for microbial colonization. Propionibacterium acnes was the sole predominant bacterial species in both sebaceous and non-sebaceous areas. Non- P. acnes species were present in approximately 30% of all colonized samples. . Only hair follicles and stratum corneum were colonized. Understanding of cutaneous microbiota requires validation from a variety of approaches and techniques.

[A recurrent case of adult favus successfully treated with terbinafine]. / Terbinafi n ile basarili olarak tedavi edilen bir eriskin nüks favus olgusu.

Favus or tinea capitis favosa, is a chronic inflammatory dermatophytosis of the scalp. The disease is particularly common in children aged 6 to 10 years, more often in boys, and it also occurs in adults. Human-to-human transmission is therefore possible. Anthropophilic Trichophyton schöenleinii is responsible for over 95% of favus cases. In addition, there are rare cases of anthropophilic T.violaceum, zoophilic (T.verrucosum, T.quinckeanum, and Microsporum canis) and geophilic M.gypseum species recorded as agents of favus. It is also reported in mice (T.quinckeanum), poultry (M.gallinae), and cats (M.incurvatum). Favus is common in Iran, Nigeria, and China, however it has been reported rarely in the last two decades in Turkey. Although Turkish records are not sufficient to indicate an accurate incidence rate, favus is still present in Turkey. In this report, a 20-year-old female with favus was presented. She had squames and areas of alopecia on the right frontoparietal area of her scalp. Scalp biopsy and hair follicle samples were taken for histopathological examination and fungal culture. According to the conventional identification by mycological methods and internal transcribed spacer (ITS) sequencing analysis, the pathogen was identified as T.schöenleinii. The patient was treated with oral terbinafine (250 mg/day) for 4 weeks and topical isoconazole and ketoconazole for 6 weeks. Clinical recovery was observed after 6 weeks, however, fungal culture could not be repeated. Six months after the initial presentation, the patient's symptoms recurred due to the poor adherence and T.schöenleinii was repeatedly grown in culture. Antifungal treatment was administered with the same drugs for the same period. There was a clinical and mycological recovery 8 months after initial presentation. Favus, which is not frequently observed in adults, is an uncommon disease. Confusion arises in its diagnosis because other diseases have similar clinical appearances, and asymptomatic carriage have also been reported. For these reasons, and because of improvements in health conditions, treatment might be delayed. With accurate assessment of the patient's medical history, the clinical characteristics of the disease, and results of laboratory analyses, coupled with effective mycologist-clinician collaboration, it is possible for the patient to continue a healthy social life. Consequently, favus is still an important health problem encountered in Turkey.

Demodex mites.

Demodex mites are normal inhabitants of human hair follicles. D folliculorum is found predominantly in the follicular infundibulum of facial skin and is typically present in small groups. D brevis, the smaller of the two species, predominates on the trunk, typically as solitarily mites within the sebaceous glands and ducts. In a wide variety of animals, Demodex mites are recognized as a cause of mange. The role of Demodex mites as agents of human disease has been more controversial, but evidence favors their involvement in acneiform eruptions, folliculitis, and a range of eruptions in immunosuppressed patients.

Three dimensional distribution of Propionibacterium acnes biofilms in human skin.

Propionibacterium acnes is regarded as a common member of the human skin microbiota, often occurring in biofilms. Little is known about the size of bacterial biofilms in hair follicles as a few sections of biopsy tissue are routinely evaluated. Transversal sectioning provides a better opportunity for histological analyses of hair follicles which can be followed through the different morphological levels. Direct visualization of P. acnes biofilms in hundreds of consecutive sections allowed insight into the 3D distribution in human hair follicles as well as investigating the depth of biofilm distribution within hair follicles. Four distinct colonization patterns of P. acnes biofilms were revealed. Results have shown that an individual P. acnes biofilm can spread for 1900 µm in a terminal hair follicle. This information can be of help while designing potential antibiofilm treatment.

Hidradenitis suppurativa: A practical review of possible medical treatments based on over 350 hidradenitis patients.

Hidradenitis suppurativa (HS), a pathological follicular disease, impacts patients' lives profoundly. HS most commonly involves cutaneous intertriginous areas, such as the axilla, inner thighs, groin and buttocks, and pendulous breasts, but can appear on any follicular skin. Protean, HS manifests with variations of abscesses, folliculitis, pyogenic granulomas, scars (oval honeycombed), comedones, tracts, fistulas, and keloids. The pathophysiology might involve both defects of the innate follicular immunity and overreaction to coagulase negative Staphylococcus. Treatment depends on the morphology, extent, severity, and duration. Topical clindamycin and dapsone are often adequate for treating mild HS. For Stage 1 and 2 HS, first line treatment combines rifampin with either oral clindamycin or minocycline. Other HS treatments include: fluoroquinolones with metronidazole and rifampin, oral dapsone, zinc, acitretin, hormone blockers (oral contraceptive pills, spironolactone, finasteride, and dutasteride), and oral prednisone. For severe HS, cyclosporine, adalimumab, or infliximab (used at double psoriatic doses) and intravenous carbapenems or cephalosporins are often required. Isotretinoin, etanercept, isoniazid, lymecycline, sulfasalazine, methotrexate, metformin, colchicine, clarithromycin, IVIG, and thalidomide are less favored treatments. The role of botulinum toxin is uncertain. The most important life style modification is weight loss. De-roofing fluctuant nodules and injection of intralesional corticosteroids ameliorates the disease and perhaps, if done at regular intervals, improves HS more permanently. Surgical excision and CO2 laser ablation are more definitive treatments. The 1064 nm laser for hair removal aids in the treatment of HS. This article centers on medical therapies and will only passingly mention surgical and laser treatments. This article summarizes my treatment experience with over 350 HS patients.

Hair loss in pityriasis versicolor lesions: a descriptive clinicopathological study.

BACKGROUND: We have observed that hair thinning and/or loss occur at times as a presenting symptom or sign in patients with pityriasis versicolor (PV). OBJECTIVE: Our objective was to verify and explore this clinical observation and depict its underlying pathology. METHODS: A total of 39 patients with PV were examined during a period of 11 months and skin biopsy specimens were taken from lesional and nonlesional skin. Hematoxylin-eosin- and periodic acid-Schiff-stained sections were examined and described. Results were statistically analyzed. RESULTS: Hair loss and/or thinning within PV lesions was shown in 61.5% of patients (P value < .0005), appearing most commonly on forearms, abdomen, and neck as well as the beard area (only in male participants). Histopathologically, in addition to the classically described features of PV, basal hydropic degeneration, follicular degeneration, miniaturization, atrophy, plugging, and/or hair shaft absence occurred in 46% of lesional versus 20.5% of nonlesional biopsy specimens (P value < .05); these changes appeared to be directly or indirectly related to the presence of Malassezia organisms in hair follicles and/or stratum corneum. LIMITATIONS: Some patients with PV lesions on the face did not approve facial biopsy. CONCLUSION: This study provides clinical and histopathological evidence that PV lesions may be associated with hair thinning and/or loss.

Cutaneous mycotic infections with pseudolymphomatous infiltrates.

We report on 3 patients with cutaneous mycotic infections (superficial dermatophytosis, 1 patient; trichophytia, 2 patients), who on histological examination revealed dense, superficial, and deep lymphoid infiltrates admixed with variable numbers of eosinophils and with large, atypical-looking, partly CD30-positive lymphocytes. All 3 patients had received steroid therapy (locally and/or orally) upon a clinical misdiagnosis of granuloma annulare. This unusual histopathologic presentation of cutaneous mycotic infections may be mistaken for a lymphoproliferative disorder, particularly for lymphomatoid papulosis.

Molluscum-like cutaneous cryptococcosis: a histopathological and pathogenetic appraisal.

BACKGROUND: Molluscum-like cutaneous cryptococcosis (MLCC) is characterized by hypopigmented or skin-colored papules with central umbilication. The histomorphological nuances of Cryptococcus neoformans infection that effect mimicry of molluscum contagiosum are undocumented. This histopathological study was undertaken to assess the histopathological characteristics of MLCC and to determine potential evolutionary pathogenetic mechanisms and significance. METHODS: A 5-year retrospective re-appraisal of cutaneous cryptococcosis biopsies with a clinical molluscum-like appearance. RESULTS: All 26 specimens with a molluscum-like appearance showed a dome-shaped architecture with central invagination and dermal C. neoformans of varying size and shape, with capsular fragmentation; 20 biopsies had a paucireactive appearance and 6 combined granulomatous and paucireactive foci. Twenty, two and four biopsies showed transepidermal, transfollicular and combined transepidermal and transfollicular elimination (TFE) of fungi, necrobiotic collagen and debris through the central invagination, respectively. Subepithelial neutrophils and collagen necrobiosis were identified in 8 and 14 cases each, respectively. Varying sized and shaped yeasts, capsules of varying width, capsular fragmentation and collagen necrobiosis were ultrastructurally confirmed. CONCLUSION: Transepithelial and TFE of C. neoformans, necrobiotic collagen, inflammatory cells and cellular debris account for the morphological attributes of MLCC. The eliminatory process is a potential public health hazard, serving as a vehicle for C. neoformans transfer to the exterior.

Alopecia syphilitica with detection of Treponema pallidum in the hair follicle.

Alopecia is one of the clinical manifestations of secondary syphilis. It is uncommon for hair loss to be the sole or predominant manifestation, as hair loss is the chief clinical and histologic differential diagnosis of alopecia areata. The main difference between these two entities is the detection of Treponema pallidum in syphilis. We present the case of a 24-year-old Hispanic man, human immunodeficiency virus seropositive in treatment, with tiny patches of non-cicatricial alopecia in the parieto-occipital regions of his scalp. The patient denied previous history of genital or other skin lesions. A biopsy from an alopecic patch was performed which showed an inflammatory non-scarring alopecia with a discrete lymphocytic type inflammatory infiltrate localized in the peribulbar region. There was lymphocyte exocytosis into the matrix, associated with vacuolar degeneration, and scattered apoptotic cells were observed. Plasma cells were scattered. Immunohistochemical studies showed the presence of T. pallidum limited to the peribulbar region and penetrating into the follicle matrix. To the authors' knowledge, this is the first time that spirochetes have been shown in the hair follicle in alopecia syphilitica, suggesting that the spirochetes may be pathogenetic and responsible for the alopecia.

Majocchi's granuloma of the face in an immunocompetent patient.

Majocchi's granuloma is a condition with chronic erythematous and indurated plaques that is a result of the rupture of a dermatophyte-infected infundibulum as a result of trauma. It is frequently seen on the anterior aspect of the legs of women. Herein, we present a case of Majocchi's granuloma of face, a site rarely involved, in an immunocompetent patient. Diagnosis was confirmed by histological and mycological examination. Histological examination revealed hyphae and arthrospores in the hair follicles and in the dermis with a diffuse dermal infiltrate consisting of lymphoplasmacytic cells, and focal collections of epithelioid cells, neutrophils and mild interstitial edema. Mycological examination confirmed the presence of fungus, Trichophyton rubrum, and the diagnosis of Majocchi's granuloma of the face was made. No concrete predisposing factor was found to be associated with the occurrence of the lesions on the face. However, the history of prolonged veiling of the face by a cloth by the patient, perhaps contributing to the occurrence of lesions on face, is a point of dubious significance.

Bacteria and fungi on the surface and within noninflamed hair follicles of skin biopsy specimens from horses with healthy skin or inflammatory dermatoses.

A retrospective study using light microscopy was performed to assess the prevalence of surface and follicular bacteria and fungi in skin biopsy specimens from 247 horses with inflammatory dermatoses and from 27 horses with healthy skin. Cocci were found on the surface of specimens from 23% (95% confidence interval 18%, 29%) and 7% (95% confidence interval, 0%, 19%), respectively, of horses with skin disease and horses with healthy skin. Of the nine dermatoses with at least 10 cases in our series of horses, bacterial folliculitis had a higher prevalence of surface bacteria (57%; 95% confidence interval 34%, 81%) than the other eight (which all had a prevalence < 30%). There was a significant association between the prevalence of surface cocci and the extent of epidermal hyperkeratosis. Cocci were found in the keratin of noninflamed hair follicles in only 2% of the horses with skin disease, and in none of the horses with healthy skin. Fungal poroconidia were found on the surface of 4% of the horses with skin disease, and on none of the horses with healthy skin. Yeasts were not found.

Propionibacterium acnes and the pathogenesis of progressive macular hypomelanosis.

BACKGROUND: Progressive macular hypomelanosis is a common hypopigmentation mainly on the central parts of the trunk, predominantly in young adults, especially women. It is often mistaken for pityriasis versicolor and pityriasis alba. It occurs in all races and has been described in many parts of the world. We discovered follicular red fluorescence restricted to lesional skin. We suspected a relation with a porphyrin-producing bacteria residing in sebum of the pilosebaceous duct, and we therefore performed a study in 8 patients. Observation In all biopsy specimens taken from lesional skin of 8 women, we could demonstrate gram-positive bacteria in the pilosebaceous duct, and a mild perifollicular lymphocytic infiltrate was seen. In all but 1 patient, Propionibacterium acnes was yielded from cultured biopsy specimens taken from follicular lesional skin. Healthy follicular skin did not show bacteria in histological sections, and cultures did not yield anaerobic bacteria. CONCLUSIONS: There seems to be a relation between the presence of P acnes and the hypopigmented macules. We propose that a factor is produced by these strains of P acnes, which interfere with melanogenesis. Based on these observations, we are undertaking a clinical trial to find a treatment for this troubling, intractable disease.

Pathogenesis of acne.

Acne vulgaris is a skin disorder of the sebaceous follicles that commonly occurs in adolescence and in young adulthood. The major pathogenic factors involved are hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The clinical presentation of acne can range from a mild comedonal form to severe inflammatory cystic acne of the face, chest, and back. At the ultrastructural level, follicular keratinocytes in comedones can be seen to possess increased numbers of desmosomes and tonofilaments, which result in ductal hypercornification. The increased activity of sebaceous glands elicited by androgen causes proliferation of P. acnes, an anaerobe present within the retained sebum in the pilosebaceous ducts. The organism possesses a ribosome-rich cytoplasm and a relatively thick cell wall, and produces several biologically active mediators that may contribute to inflammation, for instance, by promoting leukocyte migration and follicular rupture. In inflamed lesions, numerous neutrophils and macrophages infiltrate around hair follicles and sometimes phagocytose P. acnes. To examine the participation of neurogenic factors in the pathogenesis of acne, we quantitatively assessed the effects of neuropeptides on the morphology of sebaceous glands in vitro using electron microscopy. Substance P, which can be elicited by stress, promoted the development of cytoplasmic organelles in sebaceous cells, stimulated sebaceous germinative cells, and induced significant increases in the area of sebaceous glands. It also increased the size of individual sebaceous cells and the number of sebum vacuoles for each differentiated sebaceous cell, all of which suggests that substance P promotes both the proliferation and the differentiation of sebaceous glands. In this review, we introduce the general concept of pathogenic factors involved in acne, including typical electron microscopic findings and recent evidence of stress-induced exacerbation of acne from a neurological point of view. An improved understanding of the pathogenesis of acne should lead to a rational therapy to successfully treat this skin disease.

Colonisation status of Malassezia pachydermatis on the hair and in the hair follicle of healthy beagle dogs.

Hair and hair follicle carriage of Malassezia pachydermatis was studied in 12 healthy beagle dogs. The yeast was isolated from hair clipped from the lip region at 13 sites in nine dogs but was less frequently recovered from the interdigital spaces on the forefeet and from two sites on the trunk. Population sizes at the lip were significantly greater (P < 0.01) than those at other sites. Skin biopsy specimens were obtained from the same sites and epidermal and follicular tissues dissected following immersion in 1 M CaBr(2). Epidermal carriage of M. pachydermatis was identified in nine biopsy specimens taken from five dogs. Hair follicle carriage was identified in five skin specimens (four foot, one lip) from three dogs. This study indicates that M. pachydermatis is readily recovered from the distal hair in healthy dogs and that hair follicle carriage is infrequent or that populations are low at that site.

Human immunodeficiency virus-related primary cutaneous aspergillosis.

A 31-year-old Caucasian man with AIDS developed a crusted violaceous plaque under adhesive tape near a central venous catheter insertion site. Histological examination demonstrated a ruptured hair follicle containing collections of fungal hyphae typical of Aspergillus spp. A culture of the biopsy material grew Aspergillus fumigatus. The patient responded to removal of the catheter and the occlusive dressing, in addition to itraconazole therapy. Aspergillosis must be considered in the differential diagnosis of cutaneous lesions in human immunodeficiency virus-infected patients, in particular when the lesion occurs under adhesive tape or an occlusive dressing.

A clinical, microbiological, and histopathologic study of trichostasis spinulosa.

Trichostasis spinulosa (TSS) is a relatively common follicular disorder that can occur on the face and trunk, especially in the interscapular area. Its cause remains unclear. We examined clinically 30 patients with TSS and follicular materials extracted from each patient were examined microscopically. Bacterial culture and skin biopsy were done in 12 and 10 patients, respectively. Periodic acid Schiff (PAS) and Brown-Brenn Gram stain were used for detection of pityrosporum (malassezia) and bacteria. The interscapular area (14/30), nose (8/30), and cheek (4/30) were common sites of TSS. Pityrosporum and bacteria in the extracted follicular material were found at the rates of 82.6% and 73.3%, respectively. In histologic examination, follicular hyperkeratosis and numerous vellus hairs enveloped within keratotic sheath were common features. Pityrosporum and bacteria were found at the rate of 70% in biopsied specimens on PAS and Brown-Brenn Gram stain. In bacterial culture, Propionibacterium acne was most commonly identified in 75% (9 out of 12 patients). Pityrosporum and bacteria, especially Propionibacterium acne, were commonly found in the extracted follicular material and biopsied specimens. Thus, they may be related to the induction of follicular hyperkeratosis with retention of vellus hairs, and we suggest that these microorganisms may be one of the possible etiologic factors of TSS.