Background

Baldness evokes a variety of responses from both sexes. Alopecia is the medical term for hair loss. Not all hair loss is permanent and certainly not all forms are hereditary.

Alopecia Areata
Androgenetic alopecia (Common baldness, Pattern baldness)
Scarring Alopecia (Pseudopelade)
Telogen and anagen effluvium

Outline

Disease Associations
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/Immunohistochemistry/Electron Microscopy
Differential Diagnosis
Prognosis and Treatment
Commonly Used Terms

DISEASE ASSOCIATIONS	CHARACTERIZATION
BORAX SOLUTIONS
Association of reversible alopecia with occupational topical exposure to common borax-containing solutions William S. Beckett, etal.	J Am Acad Dermatol 2001;44:599-602 Abstract quote Boron is widely used in industrial materials, most frequently as the salt borax. Systemic exposure (eg, ingestion) to boron in boric acid been associated with reversible toxic alopecia among other manifestations. There is scant clinical literature on alopecia caused by topical exposure to boron. We observed a series of 3 patients in 2 workplaces who suffered reversible alopecia from cutaneous boron exposure. The scalp alopecia was global in 1 patient and patchy in 2 patients. Alopecia was completely reversed by elimination or reduction of exposure to boron-containing materials in all 3 patients. We conclude that occupational topical exposure to boron in solutions may cause reversible alopecia.

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
GENERAL
Nomenclature proposal for the zones and landmarks of the balding scalp. Beehner ML. 10 Railroad Place, Saratoga Springs, NY 12866, USA.	Dermatol Surg 2001 Apr;27(4):375-80 Abstract quote BACKGROUND: Up until now there has existed no precise, agreed-upon terminology for referring to the areas of the balding scalp. OBJECTIVE: A standardized nomenclature system for the areas of the balding scalp is proposed so that physicians and other paraprofessionals can have a common, precise language for communicating with each other. METHODS: The following, in its initial form, was proposed to the surgical hair restoration community in the Hair Transplant Forum International in 1998. This final proposal includes feedback and input from those physicians. RESULTS: The balding scalp is divided into three major areas: the frontal region, the midscalp, and the vertex. Additional "subregions" are also defined, and long-standing landmarks of the scalp and its borders are reviewed. A new landmark, the "vertex transition point," is proposed, to designate that point in the posterior midscalp where the plane begins to change from horizontal to vertical. CONCLUSION: It is hoped that a universal nomenclature system for the scalp will facilitate communication between hair surgeons, other medical specialties, nonsurgical hair replacement personnel, and hair stylists.
VARIANTS

 

HISTOLOGICAL TYPES	CHARACTERIZATION
GENERAL
Vertical and transverse sections of alopecia biopsy specimens: combining the two to maximize diagnostic yield. Elston DM, McCollough ML, Angeloni VL. Dermatology Service, Brooke Army Medical Center, Fort Sam Houston, Texas.	J Am Acad Dermatol 1995 Mar;32(3):454-7 Abstract quote BACKGROUND: Traditional vertical sections of scalp biopsy specimens contain few hair follicles. For this reason transverse sections of scalp biopsy specimens have been advocated. Both methods have advantages and disadvantages. We have developed a simple method that we believe offers the best of both methods. OBJECTIVE: Our purpose was to assess the impact of combining vertical and transverse sections of scalp biopsy specimens. METHODS: Two 4 mm punch biopsies are performed. One specimen is bisected vertically: half for hematoxylin-eosin (H-E) staining, half for direct immunofluorescence. The second specimen is bisected transversely and submitted for H-E. The three pieces of tissue for H-E staining are embedded in a single cassette. RESULTS: Because a biopsy specimen for direct immunofluorescence is commonly obtained in cases of alopecia, our method does not add a surgical procedure. All three pieces of tissue for H-E staining are embedded in a single paraffin block. Therefore the cost of histologic interpretation is not increased. Our diagnostic yield improved. Transverse sections were superior in cases of lupus erythematosus and lichen planopilaris with focal follicular involvement. Features of the follicular degeneration syndrome were also best demonstrated in transverse sections. Interface changes, lupus panniculitis, miniaturized hairs, and trichomalacia were better demonstrated in vertical sections. CONCLUSION: Our method exploits the advantages of both vertical and transverse sections and improves diagnostic yield without increasing cost.
Hair counts from scalp biopsy specimens in Asians Hyun-Jeong Lee, MD Seog-Jun Ha, MD Joo-Han Lee, MD Jin-Wou Kim, MD Hyung-Ok Kim, MD David A. Whiting, MD Seoul, Korea, and Dallas, Texas	J Am Acad Dermatol 2002;46:218-21 Abstract quote Background: Differences in hair density have been described according to the ethnic background in whites and blacks. Asians are known to have fewer hairs than whites. Objective: We performed this study to assess the normal values of hair counts in scalp biopsy specimens from Koreans. Methods: A total of 35 subjects with clinically normal occipital scalps (13 patients with androgenetic alopecia, 20 with patchy alopecia areata, and 2 healthy volunteers) were included. Horizontal sections of 4-mm punch biopsy specimens from clinically normal occipital scalps were examined at various levels from the papillary dermis to the subcutis, and follicular counts of terminal/vellus hairs and anagen/telogen hairs were obtained. Results: The numbers of total hairs, terminal and vellus hairs, and terminal anagen hairs were significantly lower (P < .05) in Koreans compared with the published data of whites and blacks. Percent ratio of terminal anagen and telogen hairs were similar to whites and blacks. Follicular density was significantly lower (P < .05) in Koreans than in whites and blacks. In Koreans, female subjects had a significantly higher number of terminal hairs than male subjects (P < .05). Conclusion: Hair density is significantly lower in Koreans than in whites or blacks. Slight sexual difference exists in follicular counts in Koreans. Our data could be used as a guideline for determining normalcy in interpreting horizontal sections of scalp biopsy specimens from Asians.
VARIANTS
FAMILIAL FOCAL ALOPECIA
Familial focal alopecia. A new disorder of hair growth clinically resembling pseudopelade. Headington JT, Astle N.	Arch Dermatol 1987 Feb;123(2):234-7 Abstract quote A 14-year-old girl was evaluated for patchy hair loss present from early childhood. Her mother was found to have a similar condition. When studied in transverse section, biopsy specimens from both women showed marked anagen-telogen transformation that circumstantially appears to be irreversible. Preservation of telogen epithelium with absence of inflammation and scarring readily separate focal familial alopecia from the pseudopelade state and from localized alopecia areata. To our knowledge, this is the first description of a new familial disorder causing focal alopecia.
LIPEDEMATOUS ALOPECIA
Lipedematous alopecia: a clinicopathologic, histologic and ultrastructural study Kevaghn P.Fair1, Keith A.Knoell2, James W.Patterson1,2, Rebecca J.Rudd2 and Kenneth E.Greer2 1Department of Pathology, 2Department of Dermatology, University of Virginia Health Science Center, Charlottesville, Virginia, USA	J Cutan Pathol 2000;27 (1), 49-53 Abstract quote Lipedematous alopecia is a rare condition of unknown etiology characterized by a thick, boggy scalp with varying degrees of hair loss that occurs in adult black females, with no clearly associated medical or physiologic conditions. The fundamental pathologic finding consists of an approximate doubling in scalp thickness resulting from expansion of the subcutaneous fat layer in the absence of adipose tissue hypertrophy or hyperplasia. Observations by light and electron microscopy detailed in this report suggest that this alteration principally manifests by localized edema with disruption and degeneration of adipose tissue. Some diminution in the number of follicles as well as focal bulb atrophy is noted. Aberrant mucin deposition such as that seen in myxedema or other cutaneous mucinoses is not a feature. The histologic findings bear some resemblance to those seen in lipedema of the legs, a relatively common but infrequently diagnosed condition. We present a case of lipedematous alopecia with emphasis on histologic and ultrastructural features. The etiology is unknown.
TEMPORAL TRAINGULAR ALOPECIA
Clinical and histologic findings in temporal triangular alopecia. Trakimas C, Sperling LC, Skelton HG 3rd, Smith KJ, Buker JL. Dermatology Service, Walter Reed Army Medical Center, Washington, DC 20307.	J Am Acad Dermatol 1994 Aug;31(2 Pt 1):205-9 Abstract quote BACKGROUND: Temporal triangular alopecia (TTA; also called "congenital triangular alopecia") is a common disorder that is assumed to be congenital. Little is known about its histologic features. OBJECTIVE: Our purpose was to describe four new cases, review the literature, and present histologic features based on vertical and transverse sectioning. METHODS: The history, clinical features, and histologic findings of four patients with TTA are described and the relevant literature reviewed. RESULTS: Lesions of TTA are seldom congenital, and most are best described as lancet-shaped. The "bald spot" contains normal numbers of hairs, although virtually all are vellus or indeterminate follicles. CONCLUSION: Most cases of TTA appear to develop during the first few years of life, and the designation "congenital" is a misnomer. The appearance of alopecia can be best explained as a focal zone of hair miniaturization leading to vellus hair formation.
Temporal triangular alopecia acquired in adulthood. Trakimas CA, Sperling LC. Dermatology Service, Walter Reed Army Medical Center, Washington, DC, USA.	J Am Acad Dermatol 1999 May;40(5 Pt 2):842-4 Abstract quote Temporal triangular alopecia is a relatively common, nonscarring form of alopecia. Sometimes congenital, the vast majority of lesions appear during the first 6 years of life and remain stable thereafter. We report a case of temporal triangular alopecia arising during adulthood.
TRICHOTILLOMANIA
Trichotillomania. Presentation, etiology, diagnosis and therapy. Walsh KH, McDougle CJ. Indiana University School of Medicine, Indianapolis, Indiana, USA.	Am J Clin Dermatol 2001;2(5):327-33 Abstract quote Trichotillomania (TTM) is an impulse disorder, in which patients chronically pull hair from the scalp and/or other sites. Very early onset of hair pulling in children under the age of 6 may be more benign and self-limiting than the more common syndrome of late childhood onset hair pulling. While far more women and adolescent girls appear for treatment, survey studies suggest chronic hair pulling also occurs in males. Diagnosis may be complicated by patient and family denial or ignorance of the hair pulling; accurate scalp examination and biopsy can be critical. Classic scalp biopsies for TTM feature trichomalacia, pigment clumps, peribulbar hemorrhage and hair canal pigment casts, and lack lymphocytic infiltrates seen in alopecia areata. Treatment is difficult: the tricyclic antidepressant clomipramine is the most promising agent, although many patients find it difficult to tolerate at adequate dosages, and treatment response may not be maintained over the long term. More benign medications have not demonstrated efficacy in controlled studies. Augmentation with topical preparations or psychotropic medications may be helpful for patients experiencing limited efficacy or relapse. Specialized psychotherapy, known as habit reversal training, is highly recommended; however, the treatment is intensive and highly specialized. Skilled therapists are difficult to locate.
The combined utilization of clinical and histological findings in the diagnosis of trichotillomania. Bergfeld W, Mulinari-Brenner F, McCarron K, Embi C. Departments of Dermatology and Pathology, The Cleveland Clinic Foundation, Cleveland, Ohio, USA.	J Cutan Pathol 2002 Apr;29(4):207-214 Abstract quote BACKGROUND:: Trichotillomania (TM) is a chronic disorder in which patients traumatically remove their own hair in a bizarre pattern. TM histopathological findings are not well defined. METHODS:: Twenty-eight scalp biopsies of TM were reviewed. Multiple vertical sections and special stains were used to evaluate the specimens. Twenty-six patients (24 female, 2 male) were in the cohort, 2 patients had 2 sets of biopsies. RESULTS: Age range was 13^78 years (mean 41 years), most of them presented with chronic TM. Specific histological findings included trichomalacia (57%) and pigmented casts (46%). Non-specific histological findings included: follicular plugging (96%), decreased number of follicles (96%), reversed anagen:telogen ratio (86%), decreased number of sebaceous glands (68%), melanoderma (68%), increased number of fibrous tracts (64%) and vellus hairs (57%), superficial dermal inflammation (57%), evidence of hemorrhage (18%) and presence of hair granulomas (18%). CONCLUSIONS: Even though TM is often a disease of the young people, middle aged and elderly patients with TM have more often a biopsy to confirm the diagnosis. This paper suggests diagnostic criteria for TM. Specific histological findings and clinical suspicion of TM were considered major criteria, while the non-specific histological findings were considered minor diagnostic criteria for TM.

 

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
SPECIAL STAINS
ELASTIC STAIN
Elastic tissue in scars and alopecia. Elston DM, McCollough ML, Warschaw KE, Bergfeld WF. Department of Dermatology, Wilford Hall Air Force and Brooke Army Medical Centers, Fort Sam Houston, Texas 78234-6200, USA.	J Cutan Pathol 2000 Mar;27(3):147-52 Abstract quote A recent report suggests that elastic fibers appear in scars in a time-dependent fashion. This observation prompted our investigation, because we have found elastic tissue stains helpful in determining the pattern of scarring in cases of permanent alopecia. We carried out this investigation to determine if the Verhoeff-Van Gieson (VVG) elastic stain can reliably differentiate scarred from non-scarred dermis and to test our hypothesis that elastic stained sections are helpful in distinguishing lichen planopilaris (LPP) from lupus erythematosus (LE), central progressive alopecia in black females ("follicular degeneration syndrome" and "hot comb alopecia" are other terms used to describe this condition) and classic ivory white idiopathic pseudopelade. We studied histological sections from surgical scars of known duration, stained with the VVG elastic stain and VVG-stained sections of scalp biopsies from patients with established lesions of permanent alopecia. In most cases, both vertical and transverse sections were examined. In every case, the VVG stain clearly differentiated scar from the normal surrounding dermis. Distinct patterns of elastic tissue allowed for correct classification in most of the well-established cases of permanent alopecia studied. We determined that the Verhoeff-Van Gieson stain is an excellent stain to evaluate the pattern of scarring in cases of permanent alopecia and elastic tissue stains may be helpful in the histological evaluation of alopecia.
IMMUNOPEROXIDASE

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
SCARRING ALOPECIA
Scarring alopecia and the dermatopathologist. Sperling LC. Department of Dermatology, Uniformed Services University, Bethesda, Maryland 20814, USA.	J Cutan Pathol 2001 Aug;28(7):333-42 Abstract quote BACKGROUND: The evaluation of patients with cicatricial alopecia is particularly challenging, and dermatopathologists receive little training in the interpretation of scalp biopsy specimens. Accurate interpretation of specimens from patients with hair disease requires both qualitative (morphology of follicles, inflammation, fibrosis, etc.) and quantitative (size, number, follicular phase) information. Much of this data can only be obtained from transverse sections. In most cases, good clinical/pathologic correlation is required, and so clinicians should be expected to provide demographic information as well as a brief description of the pattern of hair loss and a clinical differential diagnosis. RESULTS: The criteria used to classify the various forms of cicatricial alopecia are relatively imprecise, and so classification is controversial and in a state of evolution. There are five fairly distinctive forms of cicatricial alopecia: 1) chronic, cutaneous lupus erythematosus (discoid LE); 2) lichen planopilaris; 3) dissecting cellulitis (perifolliculitis abscedens et suffodiens); 4) acne keloidalis; and 5) central, centrifugal scarring alopecia (follicular degeneration syndrome, folliculitis decalvans, pseudopelade). Not all patients with cicatricial alopecia can be confidently assigned to one of these five entities, and "cicatricial alopecia, unclassified" would be an appropriate label for such cases. CONCLUSION: The histologic features of five forms of cicatricial alopecia are reviewed. Dermatopathologists can utilize a "checklist" to catalog the diagnostic features of scalp biopsy specimens. In many, but not all, cases the information thus acquired will "match" the clinical and histologic characteristics of a form of cicatricial alopecia. However, because of histologic and clinical overlap between the forms of cicatricial alopecia, a definitive diagnosis cannot always be rendered.

Main Category	Dermal Histologic Pattern	Additional Clues	Disease
Non-inflammatory
	Normal number of follicles	Some follicles thinned and positioned higher in dermis than normal, in time, all follicles vellus	Androgenic alopecia
		Most follicles normal, few follicles in catagen or telogen	Telogen effluvium
		Trichomalacia	Trichotillomania
	Decreased number of follicles	Thickened collagen bundles in widened fibrous tracts	Traction alopecia
Inflammatory
	Lymphocytes predominate	Around base of follicles	Alopecia areata
		Around infundibula mostly-wedge shaped hypergranulosis of infundibula	Lichen planopilaris
		Around infundibula mostly-smudge appearance of dermoepidermal junction beneath epidermis thinned focally	DLE
		Nodules of lymphocytes and plasma cells at junction of dermis and subcutaneous fat, and at junction of septa and lobules	Scleroderma
	Neutrophils predominate	Signs of infectious cause and identifiable-bacteria	Folliculitis decalvans
		Signs of infectious cause and identifiable-fungal	Tinea capitis Majocchi's granuloma
		Signs of infectious cause and identifiable-viral	Zoster/Varicella/Herpes simplex
		Sinus tracts	Dissecting cellulitis
		Ulcers	Burns
		Necrosis of epidermal and adnexal epithelium	Radiodermatitis, acute
	Histiocytes and plasma cells predominate		Syphilis, secondary
	Little or no infiltrate of inflammatory cells	Discrete whorls of thin collagen bundles in deep reticular dermis	Alopecia areata, late
		Fibroplasia along thinned follicles, infundibular hypergranulosis	Lichen planopilaris, late
		Thickened basement membrane, thinned epidermis	DLE, late
		Thickened crowded bundles of collagen parallel to skin surface in reticular dermis	Scleroderma, late
		Coarse bundles of collagen and prominent venules parallel to skin surface	Burn, late
		Sclerosis throughout dermis, abnormal fibrocytes, thrombosed vessels often	Radiation dermatitis, late

PROGNOSIS AND TREATMENT	CHARACTERIZATION
PROGNOSTIC FACTORS
TREATMENT
HAIR TRANSPLANTATION
A comparative clinical and histologic study of hair transplantation using Er:YAG, Er:YAG/CO2, and standard punch techniques. Sadick NS, Shea CR, Nicholson J, Gat M, Lunievski S, Prieto VG. Department of Dermatology, Weill Medical College of Cornell University, New York, New York, USA.	Dermatol Surg 2001 Sep;27(9):807-12 Abstract quote BACKGROUND: This study compares the effects of Er:YAG laser alone, Er:YAG/CO2 laser at 5 W (low power), Er:YAG/CO2 at 10 W (high power), and standard punch techniques in 10 men with androgenetic alopecia. OBJECTIVE: To study the clinical and histologic features of hair transplantation with recipient graft defects created by a new hybrid Er:YAG and CO2 laser. METHODS: Ten male patients (mean age 34 y) with Norwood IV-VI androgenetic alopecia had hair replacement surgery with the recipient sites divided into four quadrants comparing cold stell, erbium, combined erbium low-power CO2, and combined erbium high-power CO2 technologies. Hair growth, intraoperative procedure, lateral thermal damage, and patient satisfaction were compared, utilizing each of the four stated technologies. RESULTS: The addition of CO2 laser at both low and high power settings resulted in improved hemostasis when compared with standard punch or Er:YAG laser alone. The mean hair counts were similar for the Er:YAG laser, Er:YAG/CO2 (5 W) laser, and standard punch at both 3 and 6 months after treatment. Lateral thermal damage was not significantly increased by the addition of low-power CO2 to Er:YAG. The addition of high-power CO2 (10 W) laser resulted in slightly lower mean hair counts at 3 months, but significantly decreased at 6 months (P =.05). Also, high-power CO2 laser caused significantly increased lateral damage. There were no detectable differences in hsp70 expression among the groups. CONCLUSION: The addition of 5 W CO2 laser to Er:YAG laser results in better hemostasis than Er:YAG laser alone, while not significantly diminishing mean hair counts or inducing increased lateral thermal damage.
PARATHYROID HORMONE RECEPTOR AGONIST AND ANTAGONIST
A new strategy for modulating chemotherapy-induced alopecia, using PTH/PTHrP receptor agonist and antagonist. Peters EM, Foitzik K, Paus R, Ray S, Holick MF. Department of Medicine, Boston University Medical Center, MA 02118, USA.	J Invest Dermatol 2001 Aug;117(2):173-8 Abstract quote Parathyroid hormone (PTH) related peptide (PTHrP) and the PTH/PTHrP receptor (PTH/PTHrP-R) show prominent cutaneous expression, where this signaling system may exert important paracrine and/or autocrine functions, such as in hair growth control. Chemotherapy-induced alopecia - one of the fundamental unsolved problems of clinical oncology - is driven in part by defined abnormalities in hair follicle cycling. We have therefore explored the therapeutic potential of a PTH/PTHrP-R agonist and two PTH/PTHrP-R antagonists in a mouse model of cyclophosphamide-induced alopecia. Intraperitoneal administration of the agonist PTH(1-34) or the antagonists PTH(7-34) and PTHrP(7-34) significantly altered the follicular response to cyclophosphamide in vivo. PTH(7-34) and PTHrP(7-34) shifted it towards a mild form of "dystrophic anagen", associated with a significant reduction in apoptotic (TUNEL+) hair bulb cells, thus mitigating the degree of follicle damage and retarding the onset of cyclophosphamide-induced alopecia. PTH(1-34), in contrast, forced hair follicles into "dystrophic catagen", associated with enhanced intrafollicular apoptosis. We had previously shown that an induced shift in the follicular damage-response towards "dystrophic catagen" mitigates cyclophosphamide-induced alopecia, whereas a shift towards "dystrophic catagen" initially enhanced the hair loss, yet subsequently promoted accelerated hair follicle recovery. Therefore, this study in an established animal model of chemotherapy-induced alopecia, which closely mimics human chemotherapy-induced alopecia, strongly encourages the exploration of PTH/PTHrP-R agonists and antagonists as novel therapeutic agents in chemotherapy-induced alopecia.

Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.

Hair and Nails

Last Updated 6/14/2002