[Show abstract][Hide abstract] ABSTRACT: Primary cicatricial alopecia (PCA) is a group of inflammatory hair disorders that cause scarring and permanent hair loss. Previous studies have implicated PPARγ, a transcription factor that integrates lipogenic and inflammatory signals, in the pathogenesis of PCA. However, it is unknown what triggers the inflammatory response in these disorders, whether the inflammation is a primary or secondary event in disease pathogenesis, and whether the inflammatory reaction reflects an autoimmune process. In this paper, we show that the cholesterol biosynthetic pathway is impaired in the skin and hair follicles of PCA patients. Treatment of hair follicle cells with BM15766, a cholesterol biosynthesis inhibitor, or 7-dehydrocholesterol (7-DHC), a sterol precursor, stimulates the expression of pro-inflammatory chemokine genes. Painting of mouse skin with 7-DHC or BM15766 inhibits hair growth, causes follicular plugging and induces the infiltration of inflammatory cells into the interfollicular dermis. Our results demonstrate that cholesterologenic changes within hair follicle cells trigger an innate immune response that is associated with the induction of toll-like receptor (TLR) and interferon (IFN) gene expression, and the recruitment of macrophages that surround the hair follicles and initiate their destruction. These findings reveal a previously unsuspected role for cholesterol precursors in PCA pathogenesis and identify a novel link between sterols and inflammation that may prove transformative in the diagnosis and treatment of these disorders.
PLoS ONE 01/2012; 7(6):e38449. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The patient with hair loss invariably complains “I am losing my hair,” which can mean vastly different things in different
patients. Every patient with hair loss should have the following baseline lab studies: CBC, TSH, ferritin, and vitamin D 25OH
because you do not want to miss other possible contributing factors of hair loss.
KeywordsOstia-Scalp biopsy-Patient evaluation-Hair Card-Anagen hairs-Tug Test
[Show abstract][Hide abstract] ABSTRACT: A 45-year-old man presents with extensive asymptomatic hair loss affecting most of the top of his scalp. Ten years earlier,
he was seen by a dermatologist for patchy hair loss and he remembers having much pain and itching. Scalp biopsy at that time
showed lichen planopilaris. His treatment included hydroxychloroquine 200 mg twice daily and intralesional triamcinolone acetonide.
He was lost to follow up until his current visit. Scalp examination at the present time shows complete, confluent hair loss
over the entire top of his scalp with absence of follicular markings and absence of any clinical inflammation (Fig. 9.1).
Currently, there is no clinical clue regarding the diagnosis of his original patchy hair loss. A scalp biopsy is taken.
[Show abstract][Hide abstract] ABSTRACT: We discuss a patient with central centrifugal cicatricial alopecia (CCCA) who developed severe scalp pruritus that was initially attributed to the cicatricial alopecia and ultimately diagnosed as tinea capitis. The rarity of severe pruritus in CCCA should prompt a search for a fungal infection in these patients.
[Show abstract][Hide abstract] ABSTRACT: Until recently, primary cicatricial alopecias had received little attention in the clinical and research realm. With the dramatic
increases in our knowledge of basic hair biology, new and powerful tools have become available to study these rare disorders
in ways that were previously not possible. As we have moved from traditional clinical studies and histopathology to molecular
biology, new paradigms regarding the pathophysiology of cicatricial alopecia have been developed. However, after clarifying
many previously unanswered questions, we are faced with a series of new and unanswered ones. By the time this publication
is completed, new information will be available, and we encourage the reader to stay tuned and engaged as research in cicatricial
alopecia continues to unfold.
KeywordsSebotrophic hypothesis-Research in cicatricial alopecia-Animal models (in research)-Hair follicle stem cells-Epidermal stem cells-Immunology-Peroxisomes-Lipid metabolic pathways-PPAR-gamma
[Show abstract][Hide abstract] ABSTRACT: The inflammation in dissecting cellulitis and folliculitis keloidalis is secondary to follicular rupture and the release
of sebaceous and keratinous material and hair keratin fragments. The latter incite an intense inflammatory response. The inflammation
is initially neutrophilic and later mixed with lymphocytes, plasma cells, and foreign body giant cells; granulomas may form
around the hair keratin fragments. Sinus tract formation is prominent in dissecting cellulitis and rarely found in folliculitis
keloidalis. Unlike folliculitis decalvans and tufted folliculitis in which Staphylococcus aureus is usually cultured, in the mixed group, bacterial pathogens are not usually found. Dissecting cellulitis is considered part
of the follicular occlusion triad, which includes acne conglobata and hidradenitis suppurativa. The pathogenesis of folliculitis
keloidalis is not well understood.
[Show abstract][Hide abstract] ABSTRACT: In this chapter, lichen planopilaris, Graham Little syndrome, frontal fibrosing alopecia (FFA), pseudopelade (Brocq), and
central centrifugal cicatricial alopecia are described. Two additional entities that are not primary cicatricial alopecias
are included, namely chronic cutaneous lupus erythematosus (CCLE) and keratosis follicularis spinulosa decalvans (KFSD) because
they are important to recognize and differentiate.
[Show abstract][Hide abstract] ABSTRACT: The predominantly neutrophilic group of primary cicatricial alopecias includes folliculitis decalvans and tufted folliculitis.
Clinically, the affected areas are much more inflamed than the lymphocytic cicatricial alopecias with crusting, pustules,
draining, and erythema. There is usually considerable pain, tenderness, and itching. Histologically in the early stages, the
inflammatory infiltrate consists predominantly of neutrophils. However, the infiltrate does not remain neutrophilic but rather
becomes plasma-cell rich. What other histologic features can be used as clues to a neutrophilic cicatricial alopecia that
is no longer predominantly neutrophilic? Scan the scalp biopsy with low-power light microscopy: the presence of four or more
fused follicles, and dense interfollicular inflammation and fibrosis are diagnostically useful (see Chap. 3)