Chao Chun Yang

Review of hair follicle dermal cells

Hair follicle stem cells in the epithelial bulge are responsible for the continual regeneration of the hair follicle during cycling. The bulge cells reside in a niche composed of dermal cells. The dermal compartment of the hair follicle consists of the dermal papilla and dermal sheath. Interactions between hair follicle epithelial and dermal cells are necessary for hair follicle morphogenesis during development and in hair reconstitution assays. Dermal papilla and dermal sheath cells express specific markers and possess distinctive morphology and behavior in culture. These cells can induce hair follicle differentiation in epithelial cells and are required in hair reconstitution assays either in the form of intact tissue, dissociated freshly prepared cells or cultured cells. This review will focus on hair follicle dermal cells since most therapeutic efforts to date have concentrated on this aspect of the hair follicle, with the idea that enriching hair-inductive dermal cell populations and expanding their number by culture while maintaining their properties, will establish an efficient hair reconstitution assay that could eventually have therapeutic implications.

Bald scalp in men with androgenetic alopecia retains hair follicle stem cells but lacks CD200-rich and CD34-positive hair follicle progenitor cells

Androgenetic alopecia (AGA), also known as common baldness, is characterized by a marked decrease in hair follicle size, which could be related to the loss of hair follicle stem or progenitor cells. To test this hypothesis, we analyzed bald and non-bald scalp from AGA individuals for the presence of hair follicle stem and progenitor cells. Cells expressing cytokeratin15 (KRT15), CD200, CD34, and integrin, α6 (ITGA6) were quantitated via flow cytometry. High levels of KRT15 expression correlated with stem cell properties of small cell size and quiescence. These KRT15(hi) stem cells were maintained in bald scalp samples. However, CD200(hi)ITGA6(hi) and CD34(hi) cell populations--which both possessed a progenitor phenotype, in that they localized closely to the stem cell-rich bulge area but were larger and more proliferative than the KRT15(hi) stem cells--were markedly diminished. In functional assays, analogous CD200(hi)Itga6(hi) cells from murine hair follicles were multipotent and generated new hair follicles in skin reconstitution assays. These findings support the notion that a defect in conversion of hair follicle stem cells to progenitor cells plays a role in the pathogenesis of AGA.

Histopathological differential diagnosis of keloid and hypertrophic scar

Distinguishing hypertrophic scar (HS) from keloid histopathologically is sometimes difficult because thickened hyalinized collagen (keloidal collagen), the hallmark of keloid, is not always detectable and &agr;-smooth muscle actin (&agr;-SMA), a differentiating marker of HS, is variably expressed in both forms of scar. The aim of this study was to investigate additional distinguishing features to facilitate differentiation between keloid and HS. We compared various histologic features and the expression of &agr;-SMA in 40 specimens of keloid and 10 specimens of HS. The features more commonly seen in keloids were: (a) no flattening of the overlying epidermis, (b) no scarring of the papillary dermis, (c) presence of keloidal collagen, (d) absence of prominent vertically oriented blood vessels, (e) presence of prominent disarray of fibrous fascicles/nodules, (f) presence of a tongue-like advancing edge underneath normal-appearing epidermis and papillary dermis, (g) horizontal cellular fibrous band in the upper reticular dermis, and (h) prominent fascia-like fibrous band. The last three features were found in keloid specimens only, including the ones lacking detectable keloidal collagen. Our study confirmed the diagnostic value of keloidal collagen, but it was only found in 55% of keloid specimens. &agr;-SMA expression was found in both HS (70%) and keloid (45%), thus it would not be a differentiating marker. In scars with no detectable keloidal collagen, the presence of the following feature(s) favors the diagnosis of keloid: non-flattened epidermis, non-fibrotic papillary dermis, a tongue-like advancing edge, horizontal cellular fibrous band in the upper reticular dermis, and prominent fascia-like band.

Expression of sex-determining genes in human sebaceous glands and their possible role in the pathogenesis of acne.

Background  The human skin, especially the sebaceous gland, is a steroidogenic organ similar to the gonads and adrenal cortex, possessing all the enzymes required for steroid sex‐hormone synthesis and metabolism. Factors regulating cutaneous steroidogenesis associated with disease status remain largely unknown.

Hair loss in elderly women

Hair loss in elderly women has been becoming a major topic in the daily practice of dermatology. Aging of hair follicles seems to affect hair growth and pigmentation, the molecular mechanisms of which remain to be elucidated. Further senile changes in physiology and immunity may influence the onset and course of hair diseases. Some preexisting diseases such as androgenetic alopecia usually worsen after menopause, while others, like discoid lupus erythematosus, may attenuate. Hormone surveying, especially with regard to internal androgen-producing tumors, is indicated in postmenopausal women with androgenetic alopecia of sudden exacerbation or with unusual manifestation or other virilizing signs. The prevalence of alopecia totalis and alopecia universalis appears to be much lower in postmenopausal ages as compared to earlier onset. Acute or chronic telogen effluvium is not uncommonly superimposed on androgenetic alopecia. Trichotillomania shows a marked female predominance in the senile age group with a higher rate of psychopathology. Worldwide, tinea capitis has been increasingly observed in postmenopausal women. Frontal fibrosing alopecia, giant cell arteritis and erosive pustular dermatosis involve mainly elder women leading to scarring alopecia. Alopecia induced by tumor metastasis to the scalp must be considered in women with underlying neoplasms, especially breast cancer. Overall, hair loss in postmenopausal women is often multifactorial and warrants a close inspection.

Linear lupus panniculitis of the scalp presenting as alopecia along Blaschko's lines: a distinct variant of lupus panniculitis in East Asians?

A 32‐year‐old Taiwanese man presented to our clinic with a 6‐month history of linear hair loss in a wavy and curved pattern across the parietal and occipital scalp, resembling the distribution of Blaschko’s lines. Physical examination showed interfollicular erythema and follicular plugging without skin atrophy or sclerotic change. Histopathology revealed a lymphoplasmacytic infiltrate in the perifollicular dermis and subcutis with abundant mucin deposition, consistent with the diagnosis of lupus panniculitis. Treatment with hydroxychloroquine and local steroid injection resulted in complete hair regrowth but recurrence was noted. Linear lupus panniculitis of the scalp presenting as alopecia along Blaschko’s lines had so far been reported exclusively in five East Asians. Apart from classical lupus panniculitis, it had distinct clinical and histopathological features such as younger age of onset, male predominance, reversible clinical course without scarring, fewer associations with systemic lupus erythematosus, exclusive involvement of scalp, sparse inflammatory infiltration, abundant mucin deposition, higher degree of hyaline fat degeneration and negative results of immunofluorescent studies. Therefore, we propose linear lupus panniculitis of the scalp to be a distinct variant of lupus panniculitis and should be included in the differential diagnosis for focal or linear alopecia, especially in East Asians.

Non-invasive evaluation of therapeutic response in keloid scar using diffuse reflectance spectroscopy.

The pathogenesis and ideal treatment of keloid are still largely unknown, and it is essential to develop an objective assessment of keloid severity to evaluate the therapeutic response. We previously reported that our diffuse reflectance spectroscopy (DRS) system could assist clinicians in understanding the functional and structural condition of keloid scars. The purpose of this study was to understand clinical applicability of our DRS system on evaluating the scar severity and therapeutic response of keloid. We analyzed 228 spectral data from 71 subjects with keloid scars. The scars were classified into mild (0-3), moderate (4-7) and severe (8-11) according to the Vancouver scar scale. We found that as the severity of the scar increased, collagen concentration and water content increased, and the reduced scattering coefficient at 800 nm and oxygen saturation (SaO2) decreased. Using the DRS system, we found that collagen bundles aligned in a specific direction in keloid scars, but not in normal scars. Water content and SaO2 may be utilized as reliable parameters for evaluating the therapeutic response of keloid. In conclusion, the results obtained here suggest that the DRS has potential as an objective technique with which to evaluate keloid scar severity. In addition, it may be useful as a tool with which to track longitudinal response of scars in response to various therapeutic interventions.

Hypersensitivity Syndrome and Pure Red Cell Aplasia Following Allopurinol Therapy in a Patient with Chronic Kidney Disease

OBJECTIVE: To report a rare case of combined hypersensitivity syndrome and pure red cell aplasia (PRCA) following allopurinol therapy. CASE SUMMARY: A 43-year-old woman with underlying mesangioproliferative glomerulonephritis developed fever, generalized morbilliform rash, leukocytosis with marked eosinophilia, and hepatic dysfunction 3 weeks after starting allopurinol therapy (300 mg/day for 3 days followed by 200 mg/day) for hyperuricemia and arthritis. The clinical findings were judged to be a probable drug reaction according to the Naranjo probability scale. The drug-induced hypersensitivity syndrome (DHS) resolved after withdrawal of allopurinol and initiation of systemic corticosteroid therapy. However, there was progressive worsening of anemia with reticulocytopenia; PRCA was suspected. PRCA was judged to be a possible drug reaction according to the Naranjo probability scale. The patient refused blood transfusion and bone marrow biopsy. Recombinant human erythropoietin was initiated in addition to prednisolone 15 mg daily. Eleven days later (~7 wk after allopurinol withdrawal), both the hemoglobin level and reticulocyte count began to rise. The patient consented to a bone marrow study at that time, which confirmed the presence of dysplasia involving only the erythroid lineage. DISCUSSION: Allopurinol may induce DHS, aplastic anemia, and, in rare instances, PRCA. We report the first case of PRCA concurrent with allopurinol-induced DHS in a patient with chronic kidney disease. Discontinuation of allopurinol is the first step in the treatment of such cases. The slow recovery of PRCA might be partly attributed to her underlying chronic kidney disease. CONCLUSIONS: To minimize serious DHS, proper indications for treatment and dosage adjustment should be closely observed when starting allopurinol therapy in patients with chronic kidney disease.

Leptin of dermal adipose tissue is differentially expressed during the hair cycle and contributes to adipocyte-mediated growth inhibition of anagen-phase vibrissa hair

Adipose tissue encircles the lower portion of anagen hair follicles and may regulate hair cycle progression. As leptin is a major adipokine, its level of expression from the dermal white adipose tissue during hair cycle progression was studied. The result shows that leptin level is differentially expressed during hair cycle, the lowest in early anagen phase, upregulated in late anagen phase and the highest in the telogen phase. On the other hand, leptin receptor is detected in keratin 15‐positive hair bulge epithelium of both anagen‐ and telogen‐phase hair follicles of mice pelage and vibrissa hair, and hair from human scalp. Leptin contributes to adipocyte‐mediated growth inhibition of anagen‐phase vibrissa hair as demonstrated in organ culture and coculture system. Our data suggest that leptin of dermal white adipose tissue might regulate hair growth and, therefore, hair cycle progression via leptin receptor on the hair follicle epithelium.

Late-onset alopecia areata: a retrospective study of 73 patients from Taiwan.

Background  Alopecia areata (AA) is regarded to be mediated by autoimmune process, and manifests as patchy non‐scarring hair loss with occult onset. Little is known about AA occurring later in life.