Aggressive CD4/CD8 Double-Negative Primary Cutaneous T-Cell Lymphoma With Dural Invasion: A Rare Presentation of Mycosis Fungoides?

ABSTRACT: Mycosis fungoides (MF) is primarily characterized by epidermotropic CD3+/CD4+/CD45RO+ memory T cells. CD4/CD8 double-negative MF is an uncommon variant with no presumed prognostic significance. Despite the variability in the clinical course and presentation of MF, most cases behave indolently. About 5% of patients, however, advance to stage IV with visceral organ involvement. Central nervous system metastasis in MF is rare with no known cases of direct central nervous system invasion by MF to date. We report an exceedingly rare locally aggressive case of CD4/CD8 double-negative MF with direct dural invasion and underline pertinent diagnostic challenges encountered in our case.

The role of the microbiome in scalp hair follicle biology and disease.

The skin surface microbiome and its role in skin diseases have received increasing attention over the past years. Beyond, there is evidence for a continuous exchange with the cutaneous immune system in healthy skin, where hair follicles (HFs) provide unique anatomical niches. Especially, scalp HFs form large tubular invaginations, which extend deeply into the skin and harbour a variety of microorganisms. The distinct immunology of HFs with enhanced immune cell trafficking in superficial compartments in juxtaposition to immune-privileged sites crucial for hair follicle cycling and regeneration makes this organ a highly susceptible structure. Depending on composition and penetration depth, microbiota may cause typical infections, but may also contribute to pro-inflammatory environment in chronic inflammatory scalp diseases. Involvement in hair cycle regulation and immune cell maturation has been postulated. Herein, we review recent insights in hair follicle microbiome, immunology and penetration research and discuss clinical implications for scalp health and disease.

Hair and Scalp Changes in Cutaneous and Systemic Lupus Erythematosus.

Cutaneous and systemic lupus erythematosus (SLE) commonly involves the hair and scalp. Alopecia can result from direct activity of disease on the scalp or from the state of physical stress in the form of telogen effluvium. Discoid lupus erythematosus and lupus panniculitis/profundus are known to cause scarring alopecia, while accumulation of recent studies has shown that non-scarring alopecia in SLE may have different subtypes, comprising lupus erythematosus-specific and lupus erythematosus-nonspecific changes on histology. This review aims to summarize the clinical pattern, trichoscopic, histopathological, and direct immunofluorescence features of different types of alopecia in cutaneous and systemic lupus erythematosus, as well as exploring their relationship with SLE disease activity.

Inflammasome Activation Characterizes Lesional Skin of Folliculitis Decalvans.

Folliculitis decalvans (FD) is a chronic inflammatory disease leading to scarring alopecia with poorly defined pathogenesis. The aim of this study was to investigate the expression of markers associated with the activation of innate immune signals, such as inflammasome (NALP1 and NALP3), interleukin (IL)-1ß and IL-8 and type I interferon (MxA). A retrospective monocentric study was conducted and included 17 patients with FD with available biopsies. Disease activity (stable vs. active) was defined clinically and histologically. Immunostaining was performed using antibodies directed against NALP1, NALP3, IL-1ß, IL-8, and MxA on FD skin biopsies. Results were compared with normal controls and lichen planopilaris. Eleven patients had active disease and 6 had stable disease. NALP1, NALP3, and IL-1ß expression were significantly increased in hair follicles in FD compared with controls and lichen planopilaris. This study highlights the predominant immune signal associated with inflammasome activation in FD, suggesting the use of IL-1ß blockade in FD.

Scalp infection by Candida Albicans in an immunocompetent patient: a description of a rare case.

Candida is a large genus of yeast, consisting of about 150 species, among which C.albicans is the most prevalent fungal species of the human microbiota. C. albicans is the most important fungal opportunistic pathogen that can cause infection when the host becomes debilitated or immunocompromised. We report a case of a scalp infection by C.albicans in a patient without an obvious immunocompromised state.

Centrifugal lipodystrophy of the scalp manifesting as centrifugal lipodystrophic alopecia.

Centrifugal lipodystrophy (CLD), characterized by a depressed lesion in the abdominal skin, is a chronic disease occurring more often among younger patients of East Asian descent. We present an extremely unusual case of CLD of the scalp associated with reversible hair loss. The patient demonstrated alopecia in the frontal, temporal and occipital areas of the scalp, which connected to form a ring-shaped area of hair loss. Curiously, the area of hair loss gradually expanded outwards while the central region showed normal hair regrowth. Immunohistochemical analysis demonstrated reduced expression of leptin, an adipokine capable of inducing the anagen phase of the hair cycle, in the adipose tissue, associated with active inflammation. By contrast, recovery of leptin expression was observed at sites of healed inflammatory lesions, suggesting that reversible hair loss might be caused by a change in leptin expression in adipose tissue.

Vasoactive intestinal peptide, whose receptor-mediated signalling may be defective in alopecia areata, provides protection from hair follicle immune privilege collapse.

BACKGROUND: Alopecia areata (AA) is an autoimmune disorder whose pathogenesis involves the collapse of the relative immune privilege (IP) of the hair follicle (HF). Given that vasoactive intestinal peptide (VIP) is an immunoinhibitory neuropeptide released by perifollicular sensory nerve fibres, which play a role in IP maintenance, it may modulate human HF-IP and thus be therapeutically relevant for AA. OBJECTIVES: To answer the following questions: Do human HFs express VIP receptors, and does their stimulation protect from or restore experimentally induced HF-IP collapse? Is VIP signalling defective in AA HFs? METHODS: Firstly, VIP and VIP receptor (VPAC1, VPAC2) expression in human scalp HFs and AA skin was assessed. In HF organ culture, we then explored whether VIP treatment can restore and/or protect from interferon-γ-induced HF-IP collapse, assessing the expression of the key IP markers by quantitative (immuno-)histomorphometry. RESULTS: Here we provide the first evidence that VIP receptors are expressed in the epithelium of healthy human HFs at the gene and protein level. Furthermore, VIP receptor protein expression, but not VIP(+) nerve fibres, is significantly downregulated in lesional hair bulbs of patients with AA, suggesting defects in VIP receptor-mediated signalling. Moreover, we show that VIP protects the HF from experimentally induced IP collapse in vitro, but does not fully restore it once collapsed. CONCLUSIONS: These pilot data suggest that insufficient VIP receptor-mediated signalling may contribute to impairing HF-IP in patients with AA, and that VIP is a promising candidate 'HF-IP guardian' that may be therapeutically exploited to inhibit the progression of AA lesions.

Cutaneous squamous cell carcinoma of the scalp in the immunocompromised patient: review of 53 cases.

OBJECTIVE: We analyzed outcomes from immunocompromised patients with scalp squamous cell carcinoma (SCC) treated with surgical excision with and without radiation in order to explore 3-year disease-free survival and overall survival. STUDY DESIGN: The study design was a retrospective chart review. SETTING: This study was conducted in a private practice setting. SUBJECTS AND METHODS: The study included 53 immunocompromised patients with an average age of 63.2 years, with scalp squamous cell carcinoma. Pre-operative imaging dictated the extent of resection. Patients with bony involvement received wide local excision including full-thickness craniectomy and cranioplasty. Patients without bony involvement underwent wide local excision and outer-table calvarial resection. All patients were recommended to have post-operative radiation. Patients were followed for a minimum of 3 years. RESULTS: A total of 53 patients were included in the study. Six patients had pre-operative CT showing bone involvement and were treated with full-thickness craniectomy along with post-operative radiation. Fourteen patients without bone involvement on pre-operative CT were found to have positive bone involvement on final pathology. Forty-five patients underwent post-operative radiation. Patients treated with adjuvant radiation demonstrated a 3-year survival of 80 % and the overall survival was 62 %. In the surgery-only group, the 3-year survival was 62.5 % and the overall survival was 32.5 %. CONCLUSIONS: Immunocompromised patients with scalp SCC have a poor prognosis. Early detection and treatment are crucial. Based on our results, we recommend wide local excision with at least outer-table calvarial resection, and post-operative radiation. Despite aggressive therapy, patients may still have distant, local, or regional recurrence. LEVEL OF EVIDENCE: level 2b (retrospective cohort).

Imbalance of T-helper 17 and regulatory T cells in patients with alopecia areata.

There is mounting evidence that T helper (Th)17 cells and regulatory T cells (Treg) play parts in the pathogenesis of autoimmune disease. Hence, levels of these T-cell subsets in patients with alopecia areata (AA) merit investigation. Our goal was to assess Th17 and Treg levels in peripheral blood mononuclear cells (PBMC) and scalp lesions of patients with AA, correlating the findings with clinical characteristics. PBMC of 177 patients with AA (test group) and 42 healthy controls and scalp tissues of 33 patients and 15 healthy controls were collected. Levels of Th17 and Treg subsets were then determined via flow cytometry and immunohistochemical staining, correlating results in test subjects with clinical features of AA. Th17 levels were significantly higher in patients, whereas Treg levels were lower by comparison. Furthermore, Th17 levels in patients with disease of short duration or in the active phase were significantly higher, relative to their respective counterparts. Th17 levels also negatively correlated with disease duration. While Treg levels were higher in severe AA than in mild AA. Results of lesions were parallel to findings of PBMC. Our data indicates an imbalance in the immune state of patients with AA.

Histopathological investigation of clinically non-affected perilesional scalp in alopecias detected unexpected spread of disease activities.

Histopathological comparison between clinically affected and intact regions in alopecia patients has been considered to facilitate better understanding of the pathophysiology of ongoing disease. Theoretically, adjacent intact regions should provide ideal controls as they should share close histological characteristics, however, to what extent clinically non-affected neighboring regions maintain their pathological integrity has not been fully assessed. The goal of this study is to delineate histopathological characteristics of clinically intact perilesional regions in the patients with various forms of alopecia. Transverse sections of 4-mm punch biopsy at the levels of isthmus and suprabulbar portion were obtained from seemingly unimpaired perilesional scalp of 50 Japanese alopecia patients (16 alopecia areata [AA] multiplex, 19 scarring alopecia [SA], 15 other conditions) and subject to histopathological investigation. Initial screening detected decrease in anagen (anagen : telogen ratio = 82.4:17.6) when compared with previously reported standard hair counts in normal Asian scalp. This finding prompted further investigation. Unexpectedly, 33 (66%) specimens demonstrated some microscopic abnormalities, 10 (62.5%) AA specimens showed increase in telogen ratio, vellus hair count and miniaturization, while perifollicular inflammatory cell infiltration was detected in 5 (26.3%) SA cases. Exclusion of histologically affected specimens yielded average hair count numbers resembling those reported in Koreans, supporting the pathological integrity of selected samples and, more importantly, indicating normal hair counts in east Asians. These findings indicated a less recognized significance of histopathological investigation of clinically non-affected perilesional scalp in alopecias for better assessment of the spread of disease activities, which should enable better management of hair loss conditions.

Direct immunofluorescence on hair follicles--present and future perspectives.

Direct immunofluorescence (DIF) is an important tool for evaluating bullous autoimmune and connective tissue disorders. We report 21 cases of pemphigus vulgaris, bullous pemphigoid and lupus erythematosus that were investigated by performing DIF on scalp hair follicles. The study was done using a simplified technique of preparing the hairs for DIF testing. The anagen hairs tested positive in pemphigus vulgaris patients while the telogen hairs were negative. In bullous pemphigoid and lupus erythematosus cases hair DIF presented negative results.Hair DIF has the potential of taking the place of skin or mucosal DIF in pemphigus patients if performed on anagen hair follicles. The technique used to perform hair DIF is important in obtaining reliable results and eliminating the possibility of generating false-negative testing. Larger studies are needed in order to validate this method.

Analysis of the scalp of women with AIDS subjected to autopsy: epithelial, follicular, and immunologic aspects.

Hair keeps the scalp warmer and slightly moister than the rest of the skin, which contributes to a favorable environment for mycotic, bacterial, and parasitic infections. It is well established that AIDS makes the patient more susceptible to opportunistic infections and cutaneous manifestations. Because of this, the aim of this study was to analyze scalp fragments of autopsied women with AIDS. Twenty-eight scalp samples of women aged between 18 and 46 years were observed. These women were divided into 2 groups: with AIDS (n = 14) and without AIDS (n = 14). We conducted histochemical (hematoxylin-eosin, Picrosirius, and Verhoeff), morphometric (Image J; National Institutes of Health, Hamilton, ON, Canada and KS-300 Kontron-Zeiss; Kontron Elektronik, Carl-Zeiss, Germany), and immunohistochemical (S-100) analyses of the scalp. In patients with AIDS, epithelial thickness, number of epithelial cell layers, number of immature Langerhans cells in the epidermis, and percentages of elastic fibers in the dermis were significantly lower, whereas telogen hair follicles were significantly higher. The percentage of collagen fibers in the dermis and the diameter of the epithelial cells were smaller in patients with AIDS, without significant difference. AIDS possibly causes immunologic and morphologic alterations in the scalp. This study may establish parameters for better clinical and morphologic diagnostic in patients with AIDS.