Hair transplantation for the treatment of lichen planopilaris and frontal fibrosing alopecia: A report of two cases.

The efficacy of current medical treatments for lichen planopilaris (LPP) and its variant, frontal fibrosing alopecia (FFA), both lymphocyte-mediated primary cicatricial alopecias, is limited. Hair regrowth from scar tissue is usually not possible. Although hair transplantation restores the hairline and increases hair density in patients with cicatricial alopecia, the timing of the transplantation is crucial. Here, we report two Chinese patients with LPP or FFA who underwent the follicular unit extraction method of hair transplantation after the diseases were stabilised with therapy, with satisfactory results for 3-4 years of follow up.

Stress-induced premature senescence of dermal papilla cells compromises hair follicle epithelial-mesenchymal interaction.

BACKGROUND: Hair follicle is miniorgan constituted by keratinocytes and its distinctive mesenchyme of dermal papilla. Its aging is characterized by organ atrophy and impaired stem cell activation and differentiation. The contribution of dermal papilla to hair follicle aging change is not well understood. OBJECTIVE: This work was aimed at exploring the possible role of premature dermal papilla senescence in the pathogenesis of hair follicle aging. METHODS: Dermal papilla cells were challenged with H2O2 to induce premature senescence and the proliferation, apoptosis, gene expression and protein secretion were characterized. Its effect on epithelial-mesenchymal interaction was analyzed by co-culture in vitro and implantation of protein-coated beads in vivo. RESULT: Dermal papilla cells were more resistant to oxidative stress-induced apoptosis than dermal fibroblasts. The surviving dermal papilla cells showed signs of senescence but still preserved key dermal papilla signature gene expression. In addition to the failure to respond to mitogenic stimulation from keratinocytes, they lost the ability to induce hair follicle neogenesis, promoted interfollicular epidermal differentiation, inhibited follicular differentiation and, importantly, suppressed clonal growth of hair follicle stem cells. They produced higher levels of multiple inflammatory cytokines, including IL-6. Functionally, IL-6 inhibited clonal keratinocyte growth in vitro and blocked the transition from telogen to anagen in vivo. CONCLUSION: Stress-induced premature dermal papilla senescence can contribute to hair follicle aging change due to compromised epithelial-mesenchymal interaction.

Alopecia Areata After Vaccination: Recurrence with Rechallenge.

Alopecia areata (AA) is the most common form of hair loss in children. We report the case of a child who had two episodes of AA after two different vaccines with complete hair regrowth between the episodes. This case supports the concept that vaccination might be a trigger for the development of AA in genetically predisposed children.

Lymphedema-associated neutrophilic dermatosis: Two cases of localized Sweet syndrome on the lymphedematous lower limbs.

Neutrophilic dermatosis on the site of lymphedema is a rare condition and considered as a localized and less severe variant of Sweet syndrome. Only 13 cases of this variant have been reported after mastectomy for breast cancer in the English-language published work. However, this condition has never been described on the lower limbs or from other causes of lymphedema. Herein, we report two cases of localized Sweet syndrome on the lymphedematous lower limbs: one occurred after radical hysterectomy, bilateral pelvic lymph node dissection and radiotherapy for cervical cancer; the other developed after radiotherapy for malignant melanoma on the right groin. Based on clinical and histological features, we suggest the name "lymphedema-associated neutrophilic dermatosis" for this underrecognized disease entity.

Fibrous papule of the face, similar to tuberous sclerosis complex-associated angiofibroma, shows activation of the mammalian target of rapamycin pathway: evidence for a novel therapeutic strategy?

Fibrous papules of the face are hamartomas characterized by stellate-shaped stromal cells, multinucleated giant cells, and proliferative blood vessels in the dermis. The pathogenesis of fibrous papules remains unclear. There is a striking microscopic resemblance between fibrous papules and tuberous sclerosis complex (TSC)-associated angiofibromas. A germline mutation of the TSC1 or TSC2 gene, leading to activation of the mammalian target of rapamycin (mTOR) pathway, accounts for the pathogenesis of TSC-associated angiofibromas. Activated mTOR subsequently activates p70 ribosomal protein S6 kinase (p70S6K) and ribosomal protein S6 (S6) by phosphorylation. Rapamycin, a mTOR inhibitor, is effective in treating TSC-associated angiofibromas. The aim of this study was to understand whether the mTOR pathway is activated in fibrous papules. We studied immunoexpressions of phosphorylated (p-) mTOR effectors in fibrous papules, TSC-associated angiofibromas, and normal skin controls. P-mTOR, p-p70S6K and p-S6 were highly expressed in dermal stromal cells and epidermal keratinocytes in fibrous papules and TSC-associated angiofibromas but not in fibroblasts and epidermal keratinocytes of normal skin controls (p<0.001). The results suggest topical rapamycin may be a novel treatment option for fibrous papules.

Scalable production of controllable dermal papilla spheroids on PVA surfaces and the effects of spheroid size on hair follicle regeneration.

Organ size and numbers are vital issues in bioengineering for hair follicle (HF) regeneration. Murine HF dermal papilla (DP) cells are able to induce HF neogenesis when transplanted as aggregates. However, how the preparation of murine and human DP aggregates affects HF inductivity and the size of regenerated HF is yet to be determined. Here we report a scalable method for production of controllable human and rat DP spheroids in general labs for reproducible experiments. Compared with more hydrophobic polyethylene and poly(ethylene-co-vinyl alcohol), DP cells are poorly adhesive to hydrophilic polyvinyl alcohol (PVA). Seeded in PVA-coated 96-welled commercial PCR tube arrays, DP cells quickly aggregate into single spheroids with progressive compaction. Varying seeded cell numbers and culture periods enables us to control the size and cell number of the spheroids. The spheroids obtained have high viability and preserve DP characters. A proof of principle experiment was conducted to examine the size effect on the efficiency and efficacy of HF regeneration. We found that both human and rat DP spheroids are able to induce HF neogenesis and larger DP spheroids exhibit higher HF inductivity. However, the average diameter of regenerated hair fiber did not significantly change with the increasing size of transplanted DP spheroids. The result suggests that an appropriate size of DP spheroid is essential for HF inductivity, but its size cannot be directly translated to a thicker regenerated hair. Our results also have implications on the efficiency and efficacy in the regeneration of other epithelial organs.

Sebaceous carcinoma associated with seborrheic keratosis.

BACKGROUND: The association of a seborrheic keratosis with other common cutaneous neoplasms such as basal cell carcinoma and Bowen disease has been reported, but the association between a seborrheic keratotis and a malignant neoplasm with sebaceous differentiation is very unusual. OBJECTIVE: We present a case of two contiguous neoplasms, a seborrheic keratosis and a sebaceous carcinoma, and discuss the possibility of malignant change in a seborrheic keratosis as an explanation for the findings. METHODS AND RESULTS: A 57-year-old man presented with an asymptomatic tumor on the skin of his abdomen that was composed of two separate but contiguous lesions. The central lesion, about 0.9 cm in diameter, was nodular, irregular, and reddish and was surrounded by a blackish lesion about 3 cm in greatest dimension. Histopathologic examination revealed that the plaque was composed of two different adjacent tumors, including a central portion showing findings consistent with a sebaceous carcinoma and a peripheral part showing a seborrheic keratosis. CONCLUSION: Although the association is likely to be a coincidence and probably represents a collision tumor, the possibility that the sebaceous carcinoma represents malignant degeneration of the seborrheic keratosis cannot be entirely excluded.

Visualizing laser-skin interaction in vivo by multiphoton microscopy.

Recently, multiphoton microscopy has gained much popularity as a noninvasive imaging modality in biomedical research. We evaluate the potential of multiphoton microscopy for monitoring laser-skin reaction in vivo. Nude mouse skin is irradiated with an erbium:YAG laser at various fluences and immediately imaged by a multiphoton microscope. The alterations of cutaneous nonlinear optical properties including multiphoton autofluorescence and second-harmonic generation associated with laser irradiation are evaluated morphologically and quantitatively. Our results show that an erbium:YAG laser at a low fluence can selectively disrupt the stratum corneum, and this alteration may account for the penetration enhancing effect of laser-assisted transcutaneous drug delivery. At a higher fluence, the zone of tissue ablation as well as the disruption of the surrounding stratum corneum, keratinocytes, and dermal extracellular matrix can be better characterized by multiphoton microscopy as compared with conventional histology. Furthermore, the degree of collagen damage in the residual thermal zone can be quantified by second-harmonic generation signals, which have significant difference between control skin, skin irradiated with a 1.5-, 8-, and 16-J/cm2 erbium:YAG laser (P<0.05). We show that multiphoton microscopy can be a useful noninvasive imaging modality for monitoring laser-skin reaction in vivo.

Prediction of heat-induced collagen shrinkage by use of second harmonic generation microscopy.

Collagen shrinkage associated with denaturation from thermal treatment has a number of important clinical applications. However, individualized treatment is hindered by the lack of reliable noninvasive methods to monitor the process of collagen denaturation. We investigate the serial changes of collagen denaturation from thermal treatment of rat tail tendons at 58 degrees C by use of second harmonic generation (SHG) microscopy. We find that rat tail tendon shrinks progressively from 0 to 9 min of thermal treatment, and remains unchanged in length upon further thermal treatment. The SHG intensity also decreases from 0 to 9 min of thermal treatment and becomes barely detectable from further thermal treatment. Collagen shrinkage and the SHG intensity are well correlated in a linear model. In addition, SHG imaging reveals a tiger-tail-like pattern of collagen denaturation. The bands of denatured collagen progressively widen from increased thermal treatment and completely replace the adjacent bands of normal collagen after 9 min of thermal treatment. Our results show that collagen denaturation in rat tail tendon from thermal treatment is inhomogeneous, and that SHG intensity can be used to predict the degree of thermally induced collagen shrinkage. With additional development, this approach has the potential to be used in biomedical applications.