Examining Hair Loss in Women - Female Alopecia: Guide to Successful Management 2013th Edition

Female Alopecia: Guide to Successful Management 2013th Edition

2. Examining Hair Loss in Women

Ralph M. Trüeb¹

(1)

Center for Dermatology and Hair Diseases, Wallisellen, Switzerland

Abstract

As with any medical problem, the female patient complaining of hair loss requires a comprehensive medical and drug history, physical examination of the hair and scalp, and appropriate laboratory evaluation to identify the cause. The clinician also has a host of diagnostic techniques that enable classification of the patient’s disorder as a shedding disorder or a decreased density disease and documentation of true pathology or only perceived pathology.

The first, never to accept anything for true which I do not clearly know to be such; that is to say, carefully to avoid precipitancy and prejudice, and to comprise nothing more in my judgement than what is presented to my mind so clearly and distinctly as to exclude all ground of doubt.

The second, to divide each of the difficulties under examination into as many parts as possible, and as might be necessary for its adequate solution.

The third, to conduct my thoughts in such order that, by commencing with objects the simplest and easiest to know, I might ascend by little and little, and, as it were, step by step, to the knowledge of the more complex; assigning in thought a certain order even to those objects which in their own nature do not stand in a relation of antecedence and sequence.

And the last, in every case to make enumerations so complete, and reviews so general, that I might be assured that nothing was omitted.

René Descartes, Discourse on the Method of Rightly Conducting the Reason, and Seeking Truth in the Sciences (1637)

Prerequisite for delivering appropriate patient care is an understanding of the underlying pathologic dynamics of hair loss and a potential multitude of cause relationships. By approaching the hair loss patient in a methodical way, and commencing with objects the simplest and easiest to recognize, and ascending step by step to the knowledge of the more complex, an individualized treatment plan can be designed.

It must be borne in mind that hair loss often does not result from a single cause effect but from a combination of factors that all need to be addressed simultaneously for success. Therefore, it is wise to divide each of the difficulties under examination into as many parts as possible and as might be necessary for its adequate solution and finally to make enumerations so complete and reviews so general, so that nothing is omitted that might compromise success. For this purpose it is advisable to design a hair database sheet that enables a complete record of collected data.

2.1 Patient History

History taking is of paramount importance in assessing hair loss. By careful and systematic questioning, it is possible to assess the factors pertinent to differential diagnosis and particular lines of further investigation.

In the course of history taking, it is advisable never to accept anything for true, neither from the patient nor from the referring physician, which is not clearly recognizable as such, that is to say, carefully to avoid precipitancy and prejudice and to comprise nothing more in one’s judgment than what is presented to the mind so clearly and distinctly as to exclude all grounds of doubt.

2.1.1 Family History

A detailed family history relating to hair loss is pertinent to the diagnosis of genetic disorders.

While monogenic disorders are usually determined by one gene that has a strong influence on the phenotype, polygenic traits are likely to be determined by a large number of genes that confer variable levels of risk. Moreover, complex polygenic traits usually are not binary in nature; that is, the trait does not exist as one state or the other, such as affected or not affected. More so, the trait presents as a continuous variable that shows a normal distribution across a population. Ultimately, genetic sequence variation is not the only contributing factor that determines the trait. Environmental influences also play a role. It is this synergistic interplay between genes and environment that determines a complex phenotype.

Examples for monogenetic disorders leading to hair loss are hereditary hypotrichosis simplex and Marie Unna hereditary hypotrichosis:

· Hereditary hypotrichosis simplex is a rare form of hereditary hypotrichosis with no associated abnormality or hair shaft anomaly. Affected individuals typically show normal hair at birth, but diffuse hair loss and thinning of the hair shaft start during early childhood and progress with age (Fig. 2.1). In 2000, we reported on a three-generation Italian family with dominant transmission of a form of hereditary hypotrichosis simplex. The nine affected adults presented with sparse, thin, and short hair. Somewhat less sparse and longer hair was observed in the two affected young children in the third generation. We mapped the gene locus to 18p11.32-p11.23. The locus represented the first chromosome region shown to be associated with hereditary hypotrichosis simplex.

Fig. 2.1

Monogenetic trait: hereditary hypotrichosis simplex in father and daughter

· Marie Unna hereditary hypotrichosis is distinguished from hereditary hypotrichosis simplex by the presence of a peculiar twisting hair dystrophy. Characteristically coarse, wiry, twisted hair develops in early childhood and is followed by the development of alopecia beginning in the crown area (Fig. 2.2a–d). The gene locus has been mapped to 8p21.3.

Fig. 2.2

Monogenetic trait: Marie Unna hereditary hypotrichosis. (a) Coarse hair in child. (b) Initial vertex alopecia in child. (c) Established vertex alopecia in mother (With courtesy of M. Wyss, M.D.). (d) Twisting dystrophy of hair (With courtesy of M. Wyss, M.D.)

In everyday clinical practice, we are usually dealing with androgenetic alopecia that represents a complex polygenic trait. Much research concerns the genetic component of androgenetic alopecia. Research indicates that susceptibility to androgenetic alopecia is largely X-linked and related to the androgen receptor. Other genes that are not sex linked are also involved, however. Additionally, epigenetic variations that are modifiable by the environment contribute to striking phenotypic variations between individuals who have a similar genetic makeup. In summary, predisposition to balding is a polygenic trait, in which clinical expression represents a threshold effect. Therefore, the risk of premature hair loss usually rises with the frequency and extent of the balding trait within first-degree relatives (Fig. 2.3), while a negative family history does not exclude the diagnosis in a particular individual.

Fig. 2.3

Complex polygenetic trait: androgenetic alopecia in mother (left) and daughters

There is circumstantial evidence that alopecia areata represents yet another complex polygenic trait. Epidemiological studies provide evidence for involvement of alopecia areata susceptibility and severity genes. Alopecia areata with similar times of onset or similar hair loss patterns has been reported in monozygotic twins, and families with several generations of alopecia areata affected individuals suggest the condition may be a genetically determined disease. Typically 10–20 % of patients with alopecia areata indicate at least one other affected family member (Fig. 2.4). The triggers for the onset of alopecia areata may be environmental, but the resistance of the alopecia areata lesion to treatment, its persistence and regression, and its extent over the body may be influenced by the presence and interaction of multiple genes.

Fig. 2.4

Complex polygenetic trait: alopecia areata in son and father

2.1.2 Personal History

The personal history encompasses on:

∎

· Date of onset of the hair loss problem

· Periodicity of hair loss

· Rate of progression

· Previous investigations and treatments

· Present and past health status

· Medications, incl. hormonal treatments (oral contraceptive, replacement therapy)

· Dietary behavior

· Associated symptoms relating to the condition of the scalp

· Hair care habits

The medical history should focus on the most frequent causes of hair loss in women:

∎

· Iron deficiency

· Thyroid disorder

· Lupus erythematosus

· Intake of drugs or of hormones (oral contraceptives, hormone replacement therapies)

Risk factors for iron deficiency are heavy menstrual bleeding (>80 mL/month), use of an IUD, history of iron deficiency anemia, and insufficient dietary iron intake (Table 2.1).

Table 2.1

Recommended daily allowances of iron per day

Age	Recommend allowances of iron (mg/day)
0–6 months	0.27
7–12 months	11
1–3 years	7
4–8 years	10
9–13 years	8
Females 14–50 years	18
51 years and older	8
Pregnant females all ages	27
Lactating females age 14–18 years	10
Lactating females over age 19 years	9

The symptoms of iron deficiency include fatigue and decreased exercise tolerance; signs of severe anemia include skin and conjunctival pallor, tachycardia, and low blood pressure; dermatologic findings include cheilosis and koilonychia. It must be noted however that some patients with iron deficiency and even anemia may remain completely asymptomatic.

In comparison, other deficiency disorders are infrequent causes of hair loss. These include protein–calorie malnutrition, biotin deficiency, and zinc deficiency.

Protein–calorie deficiency is predominantly seen in the chronically ill and hospitalized patients; children with cystic fibrosis and gastrointestinal disease and on protein-restricted diets for management of urea cycle disorders; infants on milk-restricted diet because of suspected lactose intolerance or milk protein allergy; adolescents with anorexia nervosa; and patients with chronic renal failure, severe neurologic impairments, and malignancy.

Biotin deficiency is rare, since biotin is synthesized by intestinal bacteria. It is predominantly seen in association with parenteral nutrition without biotin supplementation in patients with short-gut syndrome, altered intestinal flora (following antibiotic treatment), and excessive ingestion of raw egg white. Two forms of hereditary biotin deficiency are known: early-onset (neonatal) holocarboxylase deficiency and late-onset (3 months) biotinidase deficiency with a characteristic organic aminoaciduria, neurologic symptoms (seizures, ataxia, optic atrophy, neurosensory hearing loss), recurrent infections, periorificial dermatitis, blepharoconjunctivitis, and alopecia (Table 2.2).

Table 2.2

Recommended supplementation dosage of biotin

Indication	Daily dosage of biotin
Biotinidase deficiency	10–40 mg daily
Holocarboxylase deficiency in pregnancy	10 mg daily
Holocarboxylase deficiency	Intravenous, solution: 18.4 μmol daily
Parenteral alimentation-induced deficiency	0ral, solution or tablet: 0.1–1 mg daily
Brittle nail disorders	2.5 mg two to three times daily
Nutritional supplementation	30–300 μg daily

Zinc deficiency is uncommon, since the daily requirement of 8–10 mg/day is usually obtained in a normal diet. Deficiency in zinc is predominantly seen in patients with chronic alcoholism, anorexia nervosa, and impaired absorption due to a diet with high phytate content, drugs that chelate zinc (ACE inhibitors), in association with pancreatitis, and in association with gastrointestinal bypass surgery. Acrodermatitis enteropathica is a rare inborn disorder with zinc malabsorption resulting in severe zinc deficiency and manifesting at time of weaning. Besides alopecia, cutaneous manifestations of zinc deficiency are acral and periorificial dermatitis (Fig. 2.5) with characteristic histopathologic findings, susceptibility to infections with Candida spp. and Staph. aureus, blepharoconjunctivitis, angular cheilitis, and stomatitis.

Fig. 2.5

Cutaneous manifestations of zinc deficiency: alopecia and peculiar acrodermatitis

Though it would appear that on a typical Western diet, the hair follicle should have no problem in producing an appropriate hair shaft, vitamin and nutritional deficiencies are not uncommon, especially in the elderly population. Socioeconomic status and functional ability have an important influence on nutritional status. When financial concerns are present, meals are skipped and food that is purchased may not provide a nutritionally adequate diet. Declines in both physical and cognitive functional status affect an individual’s ability to shop for food and to prepare meals. Nutritional problems are further compromised by social isolation, which commonly leads to apathy about food and decreased intake.

Ultimately, the older person has experienced change and loss through retirement, disability and death of friends and family, as well as change in financial, social, and physical health status. These changes may lead to depression. Depression is often unrecognized in older persons. Malnutrition may be a presenting symptom of depression in the elderly.

Thyroid dysfunction probably represents the second most frequent disorder related to hair loss in women: Hypothyroidism results from a deficiency of thyroid hormones. It is caused most commonly by chronic autoimmune thyroiditis (Hashimoto’s disease) or by iatrogenic thyroid ablation (I131 therapy or surgical thyroidectomy). Iodine deficiency is rare in developed countries, but is common in some regions of the world. Hypothyroidism is about ten times more frequent in women than in men and particularly affects women between the ages of 40 and 60 years. Early hypothyroidism is often asymptomatic and can have very mild symptoms (Table 2.3). Dull, coarse, brittle hair or diffuse alopecia may be present with particular thinning of the lateral eyebrows. The hair growth rate is slowed, with an increase in the proportion in telogen. The alopecia is of very gradual onset. Long-standing hypothyroidism may be associated, in the genetically predisposed, with androgenetic alopecia. The mechanism is presumed to be due to an increase in plasma free androgens. Such symptoms may easily be overlooked or ascribed merely to aging.

Table 2.3

List of clinical symptoms of hypothyroidism

Early:

Cold intolerance, increased sensitivity to cold

Constipation

Weight gain and water retention

Bradycardia (low heart rate – fewer than 60 beats per minute)

Fatigue

Decreased sweating

Muscle cramps and joint pain

Dry, itchy skin

Thin, brittle fingernails

Depression

Poor muscle tone (muscle hypotonia)

Female infertility, any kind of problems with menstrual cycles

Galactorrhea

Late:

Goiter

Slow speech and a hoarse, breaking voice – deepening of the voice can also be noticed

Dry puffy skin, especially on the face

Thinning of the outer third of the eyebrows (sign of Hertoghe)

Abnormal menstrual cycles

Low basal body temperature

Uncommon:

Impaired memory

Impaired cognitive function (brain fog) and inattentiveness

A slow heart rate with ECG changes including low voltage signals. Diminished cardiac output and decreased contractility

Sluggish reflexes

Hair loss

Difficulty swallowing

Shortness of breath with a shallow and slow respiratory pattern

Increased need for sleep

Irritability and mood instability

Yellowing of the skin (carotoderma)

Acute psychosis (myxedema madness) (a rare presentation of hypothyroidism)

Decreased sense of taste and smell (anosmia)

Puffy face, hands, and feet (late, less common symptoms)

Deafness

Enlarged tongue

Hyperthyroidism is due to excessive quantities of circulating thyroid hormones. Graves’ disease is by far the most common cause with an estimated prevalence of 5.9 % in a population of patients 60 years and older. Again, it is a disease of autoimmune origin affecting women much more frequently than men. The most common symptoms of hyperthyroidism are systemic rather than cutaneous and due to a hypermetabolic state known as thyrotoxicosis. Hyperthyroidism usually begins slowly. At first, the symptoms may be mistaken for simple nervousness due to stress. If one has been trying to lose weight by dieting, one may be pleased with weight loss success until the hyperthyroidism, which has quickened the weight loss, causes other problems. Diffuse hair loss is present in 20–40 % and axillary hair loss in 60 %. The severity of alopecia does not correlate with the severity of thyrotoxicosis; moreover, hair loss may alternatively be related to the medical treatment of hyperthyroidism with thyrostatics. The hair itself is fine, soft, straight, and allegedly unable to retain a permanent wave. In comparison, other endocrine disorders are infrequent causes of hair loss.

Lupus erythematosus is a systemic autoimmune disorder associated with polyclonal B-cell activation, resulting in diverse patterns of autoantibody production and a heterogeneous clinical expression constituting a spectrum extending from cutaneous disease (cutaneous lupus erythematosus) to a life-threatening systemic disease process (systemic lupus erythematosus). The clinical characteristics of cutaneous lupus erythematosus are well defined in terms of morphology, and for the classification of systemic lupus erythematosus, clinical and laboratory criteria are available. The American College of Rheumatology (ACR) established 11 criteria as a classificatory instrument to operationalize the definition of systemic lupus erythematosus in clinical trials (Table 2.4). For the purpose of identifying patients for clinical studies, a person has systemic lupus erythematosus if any 4 out of 11 symptoms are present simultaneously or serially on two separate occasions.

Table 2.4

Systemic lupus erythematosus ACR criteria

Criteria:	Sensitivity (%)	Specificity (%)
1. Malar rash (rash on cheeks)	57	96
2. Discoid rash (red, scaly patches on skin that cause scarring)	18	99
3. Serositis: pleurisy or pericarditis (pleural is more sensitive, cardiac is more specific)	56	86
4. Oral ulcers (includes oral or nasopharyngeal ulcers)	27	96
5. Arthritis: nonerosive arthritis of two or more peripheral joints, with tenderness, swelling, or effusion	86	37
6. Photosensitivity (exposure to ultraviolet light causes rash or other symptoms of disease flare-ups)	43	96
7. Hematologic disorder: hemolytic anemia (low red blood cell count) or leukopenia (white blood cell count <4,000/μl), lymphopenia (<1,500/μl) or thrombocytopenia (<100,000/μl) in the absence of offending drug	59	89
8. Renal disorder: more than 0.5 g/day protein in urine or cellular casts seen in urine under a microscope	51	94
9. Antinuclear antibody test positive	99	49
10. Immunologic disorder: positive anti-Smith, anti-ds DNA, antiphospholipid antibody and/or false-positive serological test for syphilis. Presence of anti-ss DNA in 70 % of cases (hypocomplementemia is also seen, due to consumption of C3 and C4 by immune complex-induced inflammation or to congenitally complement deficiency, which may predispose to systemic lupus erythematosus)	85	93
11. Neurologic disorder: seizures or psychosis	20	98

The many different types of skin lesions encountered in patients with lupus erythematosus have been classified into those that are histologically specific for lupus erythematosus and those that are not; this also applies to the involvement of the scalp and hair. The typical skin lesion of lupus erythematosus-specific disease on the scalp is discoid lupus erythematosus. Scalp involvement occurs in 60 % of discoid lupus erythematosus patients and is the only area involved in approximately 10 %. Patients with systemic disease may also have discoid lesions, including the scalp, though less frequently. Nevertheless, because of the high specificity of the discoid lesion, it has been included in the criteria for the classification of systemic lupus erythematosus. Of patients presenting with discoid lesions, 5–10 % develop clear-cut evidence of systemic disease, with the extent and distribution of the discoid lesions determining the risk: Patients with lesions both above and below the neck (generalized discoid lupus erythematosus) have a higher rate of immunological abnormalities and risk for progression to systemic disease compared to patients with discoid lesions restricted to the head-and-neck area (localized discoid lupus erythematosus). Patients with only discoid lesions of the scalp uncommonly progress to systemic disease. In addition to the focal and scarring form of alopecia associated with the discoid lupus erythematosus lesion, systemic lupus erythematosus patients may experience a diffuse, non-scarring, and transient hair loss associated with exacerbations of their lupus disease process. This diffuse hair loss seen in systemic disease is usually the result of a telogen effluvium. The telogen effluvium is in all probability the result of both severe catabolic effects and elevated levels of circulating pro-inflammatory cytokines of the lupus disease flare on hair growth cycling. In comparison, other connective tissue disorders are infrequent causes of hair loss.

Finally, a history of the following should be taken:

∎

· Stressful life events

· UV exposure

· Cigarette smoking

· Alcohol abuse

· Drug abuse

· Sexual risk behavior (syphilis, HIV infection)

The literature on the subject of hair loss due to stressful life events or psychogenic effluvium has been more confounding than helpful. The presence of emotional stress is not indisputable proof of its having incited the patient’s hair loss. The relationship may also be the inverse. Nevertheless, studies do suggest that women who experience high stress are more likely to experience hair loss.

For the effects of UV exposure and cigarette smoking on the condition of the hair and scalp, see Sect. 3.7.

In a study of 196 women testing positive for HIV, hair changes were observed in 47 %, predominantly thinning of hair and dry and brittle hair.

Associated symptoms relating to the condition of the scalp are:

∎

· Greasiness (seborrhea)

· Dryness (sebostasis)

· Itchiness (pruritus)

· Dandruff

· Burning sensations or hair pain (trichodynia)

· Scratching habit (15 min of scratching will lead to breakage of hair)

2.1.3 Drug History

Drug-induced hair loss is usually a diffuse non-scarring alopecia that is reversible upon withdrawal of the drug. Only a few drugs, mainly antimitotic agents, regularly cause hair loss, whereas many drugs may be the cause of isolated cases of alopecia.

There is a long list of drugs that on occasion have been cited as causing hair loss (Table 2.5): All anticoagulant and antithyroid drugs can produce hair loss; some psychotropic drugs are likely to induce a drug-related alopecia; it has been reported that some patients taking lithium developed hair thinning; case reports with tricyclic antidepressants rarely appear in the literature; hair loss is reported secondary to some anticonvulsant agents, mainly valproic acid; among antihypertensive drugs, ACE inhibitors and systemic or topical beta-adrenoceptor antagonists (for treatment of glaucoma) should be considered as possible causes of hair loss; hair loss from nonsteroidal analgesics occurs in a very small percentage of patients; and a few isolated cases have been reported with some hypocholesterolemic or anti-infectious agents.

Table 2.5

Drugs responsible for telogen effluvium (selection)

Telogen effluvium with known or assumed mechanism:
Interference with keratinization process in the hair follicle: retinoids
Vitamin A (>50,000 I.E. daily)
Acitretin
Isotretinoin
Interference with blood flow in follicular papilla: anticoagulants
Heparin
Warfarin
Interference with cholesterol synthesis: lipid-lowering agents
Fibrates (clofibrate, bezafibrate, fenofibrate)
Lovastatin
Complexation of zinc (thiol moiety): ACE inhibitors
Captopril
Enalapril
Interference with thyroid metabolism: thyrostatics and others
Propylthiouracil
Levothyroxine
Amiodarone (antiarrhythmic)
Lithium (antipsychotic)
Androgen effect: androgens, anabolics, and progestins with androgenic effect
Mesterolone
Testosterone
Danazol
Nandrolone
Norethisterone
Levonorgestrel
Tibolone
Aromatase inhibition: aromatase inhibitors
Letrozole
Anastrozole
Formestane
Cytokine effect: interferons
Alpha interferon
Gamma interferon
Telogen effluvium with unknown mechanism (in order of indications):
Blood pressure-lowering agents (beta-blocking agents):
Acebutolol	Nadolol
Atenolol	Pindolol
Labetalol	Propranolol
Metoprolol
Topical beta-blocking agents for therapy of glaucoma:
Betaxolol	Timolol
Levobunolol
Analgesics/nonsteroidal anti-inflammatory agents:
Acetaminophen	Piroxicam
Ibuprofen	Indomethacin
Ketoprofen	Penicillamine
Naproxen	Gold and gold compounds
Psychotropic agents/antidepressives:
Amitriptyline	Haloperidol
Desipramine	Imipramine
Doxepin	Nortriptyline
Fluoxetine	Trimipramine
Antiepileptics:
Carbamazepine	Paramethadione
Clonazepam	Phenytoin
Ethotoin	Trimethadione
Mephenytoin	Valproic acid
Antibiotics/tuberculostatics:
Thiamphenicol	Isoniazid
Gentamicin	Ethambutol
Nitrofurantoin
Varia:
Chloroquine, hydroxychloroquine (antimalarials)
Albendazole, mebendazole (anthelminthic agents)
Cimetidine, famotidine, ranitidine (antacids)
Allopurinol (uricostatic agent)
Sulfasalazine (antiphlogistic/sulfonamide)
Bromocriptine (prolactin inhibitor/antiparkinson agent)
Levodopa (antiparkinson agent)
Halothane (inhalation anesthetic)

Regularly, contraceptive pills or hormone replacement therapies with progestogens that possess net androgenic activity, such as norethisterone, levonorgestrel, and tibolone, induce hair loss in genetically predisposed women. It has been proposed that in the presence of a genetic susceptibility, it is the estrogen to androgen ratio that might be responsible for triggering hair loss in women. In the same line is the observation of hair loss induced in the susceptible women by treatment with aromatase inhibitors for breast cancer.

Diagnosis of drug-induced alopecia remains a challenge. The only way to confirm it is to see if an improvement occurs after cessation of the suspected drug. This side effect must be recognized because it may be a source of poor compliance in some patients.

In general, the incidence of drug-related adverse events increases with age, due to a higher susceptibility to drug-related side effects, a higher frequency of medications, co-medications, and comorbidities in older patients.

2.1.4 History of Hair Cosmetic Procedures

Women often blame hair cosmetics for their hair loss. With few specific exceptions mentioned below, the impact of hair cosmetic procedures on hair loss in women is generally overestimated. Nevertheless, for a proper appreciation of the condition of the hair shaft and hair breakage, inquiries should be made on:

∎

· Frequency and type of shampooing

· Use of hair care products

· Hairstyling products

· Hair coloring agents

· Hair curling or hair straightening

· Hair grooming habits

The use of chemicals and heat as well as braiding, chignons, and ponytails are relevant to central centrifugal cicatricial alopecia in black women and traction alopecia.

Acute diffuse telogen effluvium may follow allergic contact dermatitis of the scalp. Out of this reason an inquiry should be done on known allergies to paraphenylenediamine (PPD) and ammonium persulfate or a history of adverse reactions to hair dyeing or bleaching.

Diffuse hair loss due to an inhibition of mitosis associated with long-term use of shampoos containing keratostatic antidandruff agents, such as selenium sulfide, has been discussed in the older literature and remains controversial.

However, absence of effects of dimethicone- and non-dimethicone-containing shampoos on hair loss rates has systematically been demonstrated.

2.2 Clinical Examination

The skin and hair are gratifying for diagnosis. One has but to look and recognize since everything to be named is in full view. Looking would seem to be the simplest of diagnostic skills, and yet its simplicity lures one into neglect. To reach the level of artistry, looking must be a skillful active undertaking. The skill comes in making sense out of what is seen, and it comes in the quest for the underlying cause, once the disorder has been named. The first look is best made without prejudices of former diagnoses and without bias of laboratory data. In many instances a specific diagnosis is made in a fraction of a second if it is a simple matter of recognition. The informed look is the one most practiced by dermatologists; it comes from knowledge, experience, and visual memory. Where the diagnosis doesn’t come from a glance, the diagnostic tests come in, that is, the dermatological techniques of examination and the laboratory evaluation.

By definition, alopecia is the acquired condition of recognizable hair loss. The word alopecia comes from Greek with reference to the loss of hair in patches in foxes afflicted with sarcoptic mange.

In case of congenital absence or lack of hair, the correct terms are atrichia and hypotrichosis, respectively.

While congenital atrichia is characterized by a total and permanent absence of hair, the hair is diffusely thinned, but present in congenital hypotrichosis. Hereditary and congenital hypotrichosis and atrichia are among the most complex areas of disorders of hair growth with several distinctive entities occurring either as an isolated defect or as a feature of a complex hereditary syndrome in association with other ectodermal defects (ectodermal dysplasia). Associated abnormal features include dysplastic or brittle fingernails, skin and tooth defects, or other abnormalities that have to be sought for systematically (for an extensive list, see Online Mendelian Inheritance in Man).

∎

In daily clinical practice, we are usually dealing with the alopecias. When examining the scalp, the distribution of hair loss, presence and characteristics of associated skin lesions, and the presence of scarring should be noted. Part widths should be measured and all abnormalities noted.

2.2.1 Pattern Recognition

Male pattern androgenetic alopecia is characterized by its typical bitemporal recession of hair and balding vertex, while female pattern androgenetic alopecia is set apart by its rather diffuse thinning of the crown and a usually intact frontal hairline (Fig. 2.6).

Fig. 2.6

Pattern recognition: diffuse thinning of crown area with intact frontal hairline in female androgenetic alopecia

Since Hamilton’s first classification attempt of male scalp hair distribution in 1951, numerous classification methods for scalp hair in men and in women have been developed and proposed. Of these, the most widely used are the Hamilton–Norwood scale (I–VII) for male pattern androgenetic alopecia and the Ludwig scale (I–III) for female pattern androgenetic alopecia. The Savin scale is a photographic depiction of gradations of scalp hair loss in women as determined by parting width. The patient’s hair is compared with eight computer-generated pictorial representations of the central scalp hair parted in the middle.

Hair loss in patches signifies either alopecia areata, trichotillomania, or the scarring alopecias.

Alopecia areata typically presents with sudden hair loss causing patches to appear on the scalp or other areas of the body (Fig. 2.7a). The skin within the patches is inconspicuous, and hair follicles are intact. Ophiasis is a form of alopecia areata characterized by the loss of hair in the shape of a wave at the circumference of the head (Fig. 2.7b). The name derives from the Greek word ophis for snake, because of the apparent similarity to a snake shape and the pattern of hair loss. Occasionally, alopecia areata may progress to complete baldness, which is referred to as alopecia totalis (Fig. 2.7c). When the entire body suffers from complete hair loss, it is referred to as alopecia universalis. It is similar to the hair loss that occurs with chemotherapy. Ophiasis, alopecia totalis, and alopecia universalis all have a poor prognostic significance.

Fig. 2.7

Pattern recognition: alopecia areata. (a) Patches of hair loss. (b) Ophiasis. (c) Alopecia totalis

In trichotillomania, the hair loss is incomplete and hair loss usually confined to one or two sites. The typical presentation in the adolescent girl or young female adult is the friar tuck form of vertex and crown alopecia or tonsural trichotillomania (Fig. 2.8a). The scalp is the most common pulling site, followed by the eyebrows and eyelashes, and only rarely the face, arms, or legs. Sometimes children may pluck the hair from their furry toys (Fig. 2.8b) and, rarely, pet animals (Fig. 2.8c), which may be a helpful clue to the diagnosis, since individuals with trichotillomania are often shameful and secretive of their hair pulling behavior. Hair is often pulled out leaving an unusual shape. Within the area of hair loss, the hair exhibits differing lengths, some are broken hairs with blunt ends and some show new growth with tapered ends, are broken at mid-shaft, or present with an uneven stubble. Scaling on the scalp is not present, overall hair density is normal, and a hair pull test is negative

Fig. 2.8

Pattern recognition: trichotillomania. (a) Tonsural trichotillomania. (b) Hair plucked from furry toy. (c) Hair plucked from furry pet

Scarring alopecias usually present with irregular patches of alopecia in which the hair follicle ostia are absent. The scarring alopecias encompass a diverse group of disorders characterized by permanent destruction of the hair follicle and irreversible hair loss. The color of the affected scalp, presence of erythema and scaling, its localization and distribution, and presence of pustules and crusting, of telangiectasia, atrophy, hypo-, or hyperpigmentation may all be helpful for making a presumptive diagnosis. Usually, a diagnostic scalp biopsy is indicated. Ultimately, the pseudopeladic state of Degosrepresents the nonspecific end stage of a variety of at least 60 types of cicatricial alopecias and is characterized by coalescent patches of ivory-colored alopecia in the absence of clinical signs of inflammation (Fig. 2.9). By definition, pseudopelade of Brocq presents from the beginning with small irregular patches of scarring alopecia in the absence of clinical inflammation and is therefore often mistaken for alopecia areata (pelade in French).

Fig. 2.9

Pattern recognition: pseudopelade

One of the most distinctive clinical presentations of a scarring alopecia is frontal fibrosing alopecia that is characterized by a band-like pattern of recession along the frontotemporal and (less commonly) occipital hairline frequently associated with a characteristic loss of eyebrows (Fig. 2.10).

Fig. 2.10

Pattern recognition: frontal fibrosing alopecia. note associated rarefaction of eyebrows

Diffuse alopecia is characterized by hair loss over the entire scalp including the sides and back of the head. Bitemporal thinning is usually most conspicuous (Fig. 2.11a), and in long-standing cases, patients tend to bring hair balls to the consultation to demonstrate the amount of hair loss (Fig. 2.11b). Temporal thinning should not be confused with the bitemporal recession of the hairline in male pattern androgenetic alopecia, since diffuse alopecia may be due to a variety of causes that have to be sought out systematically and is not genetic. Treating this type of hair loss depends on recognizing and eliminating the actual hair loss cause. In most cases, the hair regrows. Some women however may continue to experience diffuse alopecia and the scalp hair remains thin (Fig. 2.11c). Complete baldness, however, never occurs.

Fig. 2.11

Pattern recognition: diffuse alopecia. (a) Temporal thinning of hair. (b) Ball of shed hair. (c) Diffuse thinning of scalp hair

2.2.2 Black and White Felt Examination

Short, miniaturized hairs in androgenetic alopecia are easily recognized when a contrasting felt background is used. An index card with a piece of black felt glued to one side for identification of light hairs and white felt glued onto the opposite side for identification of dark hairs is used as a contrast material. Fine short hairs with tapered distal ends will project up along the edge of the felt (Fig. 2.12a).

Fig. 2.12

Diagnostic techniques. (a) Black felt examination in blond hair. (b) Assessment of hair part width. (c) Hair pull test. (d, e) Hair feathering test

2.2.3 Assessment of Hair Part Width

Assessment of scalp hair density is relevant to patients with active hair shedding or thinned hair. Hair density is frequently relative to the patient’s prior assessment of her hair. The assessment of hair part width is one attempt to compare the hair densities in different areas of the scalp or in the course of time. When hair is dense, a very fine, thin-lined part can be seen (Fig. 2.12b), while in areas of decreased density, the part line is very irregular in diameter with small clear areas on both sides of the part line.

Using a comb, a series of coronal parts can be made over the vertex and the part width compared to that in the occipital area. In general, scalp hair is less dense on the vertex, and the thinning increases with age. Widened parts over the vertex are particularly conspicuous in androgenetic alopecia and may tighten in the course of successful treatment.

2.2.4 Hair Pull

The hair pull should be done on every patient who complains of hair loss to assess quickly the amount of hair shed. A cluster of approximately 50 hairs is grasped and held at the ends of the thumb and index finger exerting a slow and constant traction sufficient to tend the scalp slightly while moving towards the distal end of the hair (Fig. 2.12c). At least two different scalp sites are pulled: in diffuse telogen effluvium or androgenetic alopecia frontal (2 cm behind the forehead and 2 cm lateral) and occipital (2 cm lateral from the occipital protuberance), in circumscribed alopecias, such as alopecia areata or trichotillomania, one sample is taken from the border zone and the control from the normal-appearing contralateral region.

Normal patients can have up to four hairs epilated per site, but six or more hairs are suggestive of effluvium.

Additional information can be obtained by examining the bulbs of the epilated hairs. They are usually telogen bulbs, increased frontally in androgenetic alopecia and occipitally in diffuse telogen effluvium. In some instances, they may be dystrophic anagen hairs, as seen in dystrophic anagen effluvium, or dysplastic anagen hairs, as seen in loose anagen hair.

2.2.5 Hair Feathering

The hair feathering test is used to determine abnormal hair fragility with hair shaft breakage and should be performed on patients who complain that their hair fails to grow or breaks off. The distal 2–3 cm of the hairs is grasped between the thumb and index finger. After rubbing the distal hair ends between the thumb and index finger, a brisk pull is made on the ends of the hairs. The thumb and index finger are then checked for short broken hair fragments (Fig. 2.12d, e).

In case of increased hair fragility in the hair feathering test, a light microscopic inspection of the hair shaft is warranted to detect the hair shaft defect underlying abnormal breakage.

2.3 Trichoscopy

The naked eye is right for the global look, but for close inspection the additional use of a magnifying glass is practiced. The handheld, single-lens magnifier is the simplest and least expensive, most commonly used by dermatologists, usually at a magnification of 3× to 4×. Although the pathologist lives in a world magnified 100–1,000 times, the clinician doesn’t benefit from a highly magnified view of the patient, lest he performs dermoscopy (10×) and is knowledgeable of the clinicopathologic correlations.

Dermoscopy is a noninvasive diagnostic tool that permits recognition of morphologic structures not visible to the naked eye. Dermatologists involved in the management of hair and scalp disorders have discovered dermoscopy to also be useful in their daily clinical practice. Scalp dermoscopy or trichoscopy is not only helpful for the diagnosis of hair and scalp disorders, but it can also give clues about the disease stage and progression.

Examination of the scalp by dermoscopy can reassure patients with hair loss that they have received a thorough scalp examination, since patients with hair loss are very distressed and often feel that they are not properly examined.

2.3.1 Using the Dermatoscope for Diagnosing Hair and Scalp Disorders

Studies suggest that the use of dermoscopy in the clinical evaluation of hair and scalp disorders improves diagnostic capability beyond simple clinical inspection and reveals novel features of disease, which may extend our clinical and pathogenetic understanding.

Therefore, dermoscopy of hair and scalp (trichoscopy) is gaining popularity in daily clinic practice as a valuable tool in differential diagnosis of hair and scalp disorders. This method allows viewing of the hair and scalp at high magnifications using a simple handheld dermatoscope (Heine Delta 20®, DermoGenius®, DermLite II PRO HR® or DermLite DL3®), with alcohol as the interface solution.

2.3.2 Patterns of Scalp Disease Revealed by Dermoscopy

Using dermoscopy, signature patterns are seen in a range of scalp and hair conditions. Some predominate in certain diseases; others can even help in making a diagnosis in clinically uncertain cases.

Tosti classified the patterns as either interfollicular or follicular. The interfollicular patterns are further subdivided into vascular and pigment patterns. Scaling can be observed either as epidermal or perifollicular scaling. Finally, the dermatoscope can also be used to visualize hair shaft disorders and exogenous materials on the hair and scalp.

2.3.3 Follicular Patterns

Follicular patterns (Fig. 2.13a–f) encompass distinctive peripilar features that relate to the condition of the hair follicle:

Fig. 2.13

Trichoscopy. (a–f) Follicular patterns. (a) Yellow dots. (b) Black dots. (c) Follicular keratosis. (d) Peripilar signs. (e) Empty follicles. (f) Loss of follicular ostia. (g–l) Interfollicular patterns (vascular, pigment). (g) Simple red loops. (h) Arborizing red lines. (i) Absent vascular loops. (j) Twisted red loops. (k) Hair needle vascular loops. (l) Honeycomb pigment pattern. (m) Scaling. (n–s) Hair shaft patterns. (n) Hair diameter diversity (anisotrichosis). (o) Dystrophic hairs (exclamation mark hair). (p) Hair tufting. (q) Monilethrix. (r) Pili torti. (s) Trichorrhexis nodosa. (t–w) Exogenous materials. (t) Hair dye. (u) Camouflage product (hair building fibers). (v) Hair spray residues. (w) Ectoparasite (head louse). (x) Ectoparasite (nit)

· Yellow dots (Fig. 2.13a) are characterized by an array of quite monomorphous, though variably sized, yellow to yellow-pink, round, or polycyclic dots that are devoid of hair or contain dystrophic or vellus hair. They correspond to dilated follicular infundibula that contain sebaceous and keratinous material. Yellow dots are a major feature of alopecia areata, where they are found in 95 % of cases. They occasionally (8 %) may also be seen in advanced androgenetic alopecia. In both conditions, they are most apparent in areas of alopecia.

· Black dots (Fig. 2.13b) represent pigmented hairs broken off at scalp level. They are seen in acute alopecia areata, tinea capitis (scalp ringworm), and trichotillomania, in which areas of alopecia are studded with follicular black dots. In alopecia areata, they represent dystrophic hairs (cadaverized hairs); in tinea capitis, the classical lesion produced by endothrix species (e.g., Trichophyton tonsurans, T. violaceum) that invade the hair shaft (black-dot ringworm); and in trichotillomania, hairs broken through the pathological hair pulling habit.

· Follicular keratosis (Fig. 2.13c) is characterized by follicular plugging with keratotic material. It may produce peripilar (keratin) casts. It is found in keratinization disorders, for example, monilethrix, but is more commonly seen as an unspecific parakeratotic reaction pattern to follicular inflammation at the level of the isthmus and infundibulum, for example, lichen planopilaris.

· Peripilar signs (peripilar cupular atrophy) (Fig. 2.13d) are characterized by the presence of a brown halo, roughly 1 mm in diameter, at the follicular ostium around the emerging hair shaft. This finding has been found to be linked to superficial perifollicular lymphocytic infiltrates in early androgenetic alopecia.

· Empty follicles (Fig. 2.13e) are characterized by empty follicular ostia. They represent the physiological interval of the hair cycle in which the hair follicle remains empty after the telogen hair has been extruded and before a new anagen hair emerges (lag phase or kenogen). During kenogen, the hair follicle rests physiologically, but duration and frequency are greater in androgenetic alopecia, possibly accounting for baldness.

· Loss of follicular ostia (Fig. 2.13f) is the hallmark of scarring alopecia. By definition scarring alopecia represents visible loss of follicular ostia with destruction of the hair follicle on histopathological examination. Classification of the scarring alopecias on the basis of pathology provides the diagnostic framework. Out of this reason, loss of follicular ostia usually represents an indication for diagnostic scalp biopsy.

2.3.4 Interfollicular Patterns (Vascular, Pigment)

Vascular features reflect differences in the skin capillary loop network in relation to the condition of the scalp:

· Simple red loops (Fig. 2.13g) are seen in a normal epidermis. The pattern is characterized by multiple, fine, red lasso- or hairpin-shaped structures that are regularly spaced.

· Arborizing red lines (Fig. 2.13h) have a wider caliber than the loops and are usually found in a focal pattern. They are seen to underlie and be associated with loops to a variable degree in normal scalp and in diseased scalp of different etiologies.

· Effaced or absent loops (Fig. 2.13i) are seen in conditions with epidermal atrophy, for example, in established chronic cutaneous lupus erythematosus, when the epidermis has atrophied.

· Twisted red loops occur in states of epidermal hypertrophy proportionate to its degree. Multiple, again relatively evenly spaced, twisted loops are a feature of psoriasis. They are also observed in about 20 % of seborrheic dermatitis and in folliculitis decalvans. Their distribution is diffuse in psoriasis (Fig. 2.13j) and concentrated in the form of hair needle vascular loops around actively affected follicles in folliculitis decalvans (Fig. 2.13k). Their number and visibility correlate with disease activity.

· Honeycomb pigment pattern is characterized by a relatively homogeneous network of adjoining brown rings observed in normal individuals with darker skin colors and in the sun-exposed scalp of light-skinned individuals with thinned hair. Its distribution is diffuse in bald scalp and multifocal when some hair remains in the area (Fig. 2.13l). Usually, the degree correlates with the degree of hair loss and sun exposure.

2.3.5 Scaling

Scaling is an unspecific feature of reactive epidermal hyperproliferation with parakeratosis. The epidermis continuously regenerates itself, and epidermal keratinocytes are pushed outward where they undergo terminal differentiation to corneocytes that eventually flake off. Normally, these flakes of skin are too small to be visible. However, inflammatory conditions of the scalp accelerate cell turnover, especially in the scalp, with abnormal keratinization. The result is that the corneocytes are shed in large clumps, which appear as white or grayish patches on the scalp (Fig. 2.13m). Depending on the cause the scales differ in localization, size, and greasiness (pityriasis simplex, pityriasis steatoides, pityriasis amiantacea). Scaling severity can be graded on a photographic scale and utilized to evaluate the effect of treatment.

2.3.6 Hair Shaft Patterns

Hair shaft patterns (Fig. 2.13n–s) reflect features that relate to the production and maintenance of the hair shaft:

· Hair diameter diversity or anisotrichosis (Fig. 2.13n) relates to the presence of hairs with different caliber. This finding is typical of androgenetic alopecia and reflects progressive hair follicle miniaturization due to this condition.

· Dystrophic hairs represent hairs that have fractured tips due to any process inhibiting cell division in the hair matrix. Severe inhibition leads to fracture if the narrowing of the hair shaft is marked. The hair shaft may be fractured before emergence from the scalp and then appears as cadaverized hair (also see black dots) or then appears as short exclamation mark hair (Fig. 2.13o).

· Hair tufting refers to the emergence of several hair shafts together from the scalp and tufted folliculitis to an inflammatory condition of the scalp that resolves with patches of scarring alopecia within which multiple hair tufts emerge from dilated follicular ostia (Fig. 2.13p). Histologically, a single tuft consists of clustering of adjacent follicular units opening at the bottom of an epidermal depression. While hair tufting to a lesser degree (usually < 5 hairs per ostium) may be found on the occipital scalp of healthy young men or represent an unspecific finding in other inflammatory scarring alopecias, that is, lichen planopilaris and dissecting folliculitis of the scalp, tufted folliculitis of the scalp is considered a distinctive clinicohistological variant of folliculitis decalvans.

· Hair shaft abnormalities result from genetic conditions and/or exogenous factors affecting the integrity of the hair shaft. Hair shaft abnormalities may occur as localized or generalized disorders and may lead to unruly hair and brittleness. Diagnosis is based on microscopic examination of the hair shaft. Dermoscopy is an effective tool for quick diagnosis of both congenital and acquired hair shaft disorders. Hair shaft abnormalities that can be visualized by dermoscopy include the following:

· Monilethrix (Fig. 2.13q) is characterized by a beaded appearance of the hair due to periodic thinning of the shaft. The uncommon hereditary condition is transmitted as an autosomal dominant trait. The phenotype results in hair fragility and patchy dystrophic alopecia. The alopecia is more severe in the occipital region that is more exposed to friction. Typically the occipital scalp also presents follicular keratosis.

· Pili torti (Fig. 2.13r) is characterized by hair that is flattened and twisted through 180° on its axis at varying intervals; the hair can additionally be grooved and has then also been termed pili torti et canaliculi. The hair shaft anomaly can be seen as an isolated hereditary trait, in a number of genetic syndromes, including Menkes kinky hair syndrome, Björnstad syndrome (with sensorineural deafness), and the ectodermal dysplasias. More commonly, it is found as acquired pili torti around the edges of patches of cicatricial alopecia, particularly lichen planopilaris, where local inflammatory and fibrosing processes distort the hair follicle.

· Pili canaliculi et trianguli refers to the triangular hair shafts with longitudinal grooving underlying the uncombable hair syndrome.

· Pili annulati is defined by a characteristic alternating light and dark banding in the hair shaft, due to air-filled spaces between the macrofibrillar units of the hair cortex. Their significance lies in that affected hair is more susceptible to weathering, particularly in combination with androgenetic alopecia. With onset of hair thinning due to androgenetic alopecia, progressive reduction of hair shaft diameter may cause increased fragility and trichorrhexis nodosa-like hair shaft fracturing.

· Trichorrhexis invaginata or bamboo hair is the marker for Netherton’s syndrome, a rare autosomal recessive condition with bamboo hair, ichthyosis, and atopic dermatitis. The hair shaft shows multiple nodes along its length. The nodes consist of a proximal cup-shaped portion and a distal ball-shaped portion, resembling the joint of bamboo. Hair breakage corresponds to the nodes. Eyebrows are affected as well as scalp hair. Simple examination of eyebrow hairs may increase the likelihood of early diagnosis of Netherton’s syndrome in the newborn with congenital erythrodermic ichthyosis.

· Trichorrhexis nodosa refers to white knots with transverse fractures along the hair shaft. Dermoscopy reveals brush-like hair fracturing (Fig. 2.13s). In general, trichorrhexis nodosa is an unspecific finding related to excess stress of hair in relation to its fragility. It can be observed in hair shaft abnormalities with increased fragility or more frequently as a consequence of hair weathering.

2.3.7 Exogenous Materials

A variety of exogenous materials of very different origin can be visualized by dermoscopy. These include hair dyes (Fig. 2.13t), camouflage products (Fig. 2.13u), residues from hair styling aids (Fig. 2.13v), and ectoparasites (Fig. 2.13w, x).

2.3.8 Summary of Dermoscopic Features in Common Conditions

∎

Androgenetic alopecia

· Hair diameter diversity (anisotrichosis)

· Peripilar signs

· Empty follicles

· Honeycomb pigment pattern

· Arborizing red lines

Alopecia areata

· Yellow dots

· Dystrophic hairs (cadaverized hairs, exclamation mark hairs)

· Short regrowing miniaturized hairs

Trichotillomania

· Coiled fractured hairs

· Longitudinally split short hairs

· Black dots

Dermoscopic features of scarring alopecias:

All

· Loss of follicular ostia

Lichen planopilaris

· Follicular keratosis

· Hair casts

· Acquired pili torti

Chronic cutaneous lupus erythematosus

· Arborizing telangiectasia

· Follicular keratotic plugs

· Scalp atrophy with effaced or absent vascular loops

Folliculitis decalvans

· Severe scaling and crusting

· Pronounced hair tufting

· Follicular pustules

· Numerous coiled capillary loops

Classic pseudopelade of Brocq

· No other changes (selective loss of follicular ostia)

2.4 Trichogram

The trichogram or hair pluck test is a semi-invasive technique for hair analysis on the basis of the hair growth cycle. It involves the forceful plucking of 50–100 hairs with a forceps from specific sites of the scalp. A major objective of trichogram measurements is to evaluate and count the status of individual hair roots and to establish the ratio of anagen to telogen roots.

Following the original description of the hair growth cycle by Anatomist Mildred Trotter (1899–1991), studies on the dynamics of the follicular cycle have largely depended on the microscopic evaluation of plucked hairs with quantitative measuring of the number of individual hair roots. The method was introduced in 1957 by van Scott et al. as an indicator of hair growth in toxicologic studies with cytotoxic agents. In 1964, the term trichogram was initially used by Pecoraro to describe several hair growth parameters, such as the growth rate, shaft diameter, and telogen rate. Subsequently, the trichogram technique was developed and standardized to serve as a diagnostic tool for evaluation of hair loss in daily clinical practice. For this purpose it is simple to perform, repeatable, and reasonably reliable under standardized conditions.

Since in 95 % of cases, hair loss is due to a disorder of hair cycling, trichogram measurements serve as a standard method for quantifying the hair in its different growth cycle phases as it relates to the pathologic dynamics underlying the loss of hair. The percentage of hair roots in anagen, catagen, or telogen reflects either synchronization phenomena of the hair cycle or alterations in the duration of the respective growth cycle phases. Finally, the presence of dystrophic hair roots signalizes a massive damage to anagen hair follicles, either by toxins or drugs in higher concentrations or in severe alopecia areata.

2.4.1 Trichogram Procedure

The trichogram technique provides reliable results under the condition that hair samples are obtained under a standardized procedure.

The materials necessary for performing a trichogram include a tail comb; hair clips; artery forceps covered with rubber tube; a pair of scissors; microslides, 76 × 26 mm; cover glasses, 50 × 24 mm; Eukitt; xylol; a dissecting needle; and a binocular microscope with variable objectives (2.5 and 4.0) (Fig. 2.14a).

Fig. 2.14

(a–o) Trichogram. (a) Materials. (b–o) Procedure. (p–t) Hair root forms. (p) Telogen. (q) Anagen with root sheaths. (r) Anagen without root sheaths. (s) Catagen. (t) Dystrophic anagen

The reproducibility of trichogram measurements relies on the adherence to strict standards in obtaining the hair samples.

Epilation of hair samples for the trichogram should always be performed at least 5 days after the last hair wash to avoid an artificial reduction of the telogen count. To avoid additional loss of telogen hairs, the hairs should also not be cut, curled, waved, or backcombed during that period.

Usually, epilations are carried out from two specified sites at the same time: in diffuse effluvium or androgenetic alopecia frontal (2 cm behind the forehead and 2 cm lateral) and occipital (2 cm lateral from the occipital protuberance); in circumscribed alopecias, such as alopecia areata or trichotillomania, one sample is taken from the border zone and the control from the normal-appearing contralateral region (Fig. 2.14b–o).

The same standardized scalp regions should always be chosen to permit an optimal comparison of trichogram results in case of a follow-up examination.

Within the chosen area for epilation, the hair is parted and fixed with clips. Along the parting line, a bundle of approximately 50–100 hairs is lifted parallel along the course of the hair and grasped close to the scalp with the forceps whose jaws are covered with the rubber tubes. The forceps jaws are pressed together to the maximum and the tuft of hair is then epilated.

A sharp quick pull and exact plucking in the direction of the emergence angle of the hairs from the scalp are important to obtain a reliable hair root pattern. Slow or hesitant traction or the wrong pulling direction may induce distortions or alterations of the plucked hairs complicating interpretation.

Embedding of epilated hairs occurs immediately to prevent dehydration of the hair roots. A few drops of Eukitt (after condensation, dilute with xylol) are given on two marked microslides. The tuft of hairs is taken with thumb and pointing finger, the roots are dipped in the embedding material (Eukitt), cut off 2 cm above the roots, and arranged in a fast manner with the dissecting needle in a parallel position before being covered. The evaluation can be done when the embedding material no longer runs, usually after 10 min. Correctly embedded hair roots are suitable for unlimited storage.

The act of plucking scalp hair may cause slight discomfort to the patient and may leave a small linear bald patch, which is why the frontal epilation site is better chosen contralateral to the natural hair part of the patient. The patient should be reassured that plucked hairs grow back after 3–6 weeks.

2.4.2 Trichogram Evaluation

The trichogram is a simple and reliable technique, but it needs critical interpretation. It provides information about the hair growth capacity, it detects disturbances of hair growth, and it detects toxic effects to the hair structure, induced by chemicals or drugs. In addition, the appearance and the size of the hair bulb are also important as atrophy and shrinkage reflect reduced growth activity. Finally, simultaneous microscopic examination of the hair shaft morphology may also help identify abnormalities of the hair shaft.

In every stage of the hair cycle, the hair root is characterized by a typical morphologic structure that is easy to recognize:

· Telogen. Telogen hairs are those hairs shed with daily combing. Telogen bulbs are normally epilated with a simple hair pull. When increased numbers of telogen hairs are shed, this suggests the diagnosis of telogen effluvium. The telogen hair root is characteristically club shaped; unpigmented, with smooth contours; and has no attached root sheath structure (Fig. 2.14p).

· Anagen with root sheaths. Anagen hairs are not normally seen in daily hair collections or epilated with a simple hair pull, with the exception of loose anagen hair that presents with anagen hairs devoid of hair root sheaths. Since anagen hairs are normal growing hairs, they must be forcibly plucked from the scalp. The normal anagen hair root has a large base with an equally large diameter throughout. The bulb tip is usually pigmented and the adjacent hair shaft has a white coating composed of both the inner and outer root sheath (Fig. 2.14q).

· Anagen without root sheaths (dysplastic anagen hair). These represent an epilation artifact in thin but obviously growing anagen hairs, with a diminished matrix diameter and devoid of hair root sheaths. The lower end of the hair shaft is usually wavy or bent like the handle of a bishop’s crozier (Fig. 2.14r).

· Catagen. The hair root in catagen generally has an equal diameter throughout or can become narrower towards the base. The hair roots look like club hair in the telogen phase, but still shows root sheaths, which increasingly become shorter (Fig. 2.14s).

· Dystrophic anagen. Under normal circumstances, dystrophic roots appear very seldom. Basically, they represent thin, nongrowing anagen hairs. Any pathologic condition that causes rapid cessation of mitosis in the hair matrix results in tapering of the diameter of the hair shaft that breaks off at the narrowest level with a pencil-like broken end tip (Fig. 2.14t).

· Broken-off hairs. They represent normally growing anagen hairs that have broken off on plucking. They can be easily recognized, since the broken ends appear smooth with a remaining diameter equal to that of the hair shaft.

· Miniature hairs. In addition to hairs of normal diameter, patients with androgenetic alopecia have a second population of hairs in the androgen-dependent area resulting from progressive narrowing and shortening of the hair shaft. These hairs represent terminal-to-vellus hair transformation. They are approximately 1 cm long and often have finely tapered tips. By definition vellus hairs have a shaft diameter of <40 μm.

2.4.3 Trichogram Interpretation

Normally a maximum of 15 % of scalp hair bulbs are in telogen and 85 % are in anagen.

Normally a maximum of 20 % of scalp hair bulbs are anagen hairs devoid of hair root sheaths (dysplastic anagen hairs).

Trichograms with >10 % broken-off hairs cannot be evaluated correctly. Unless they are due to fragile hair, plucking should be repeated (Table 2.6).

Table 2.6

Normal distribution pattern of hair roots in the trichogram of the scalp

Hair roots	Percent
Anagen with root sheaths	60–80
Anagen without root sheaths (dysplastic anagen)	5–20
Catagen	1–3
Telogen	12–15
Dystrophic anagen	<2
Broken-off hairs	5–6

From Blume-Peytaivi and Orfanos (1995)

The trichogram is diagnostic for telogen effluvium if more than 20 % of bulbs are in telogen. An increase of the frontal telogen rate together with a normal occipital telogen rate is diagnostic for androgenetic alopecia, while an increase of the occipital telogen rate is diagnostic for diffuse telogen effluvium. Normal telogen rates neither support nor exclude the diagnosis of androgenetic alopecia (Table 2.7).

Table 2.7

Causes for telogen effluvium

Postpartal effluvium

Postfebrile effluvium

Postinfectious effluvium

Effluvium in chronic diseases and malignancies

Effluvium in iron deficiency

Effluvium from endocrinologic diseases

Effluvium induced by cytostatic, anticoagulant, or chemical substances or ionizing radiation in low doses

Alopecia areata with slow progression

Androgenetic alopecia

Psychogenic effluvium

Modified from Braun-Falco and Heilgemeir (1985)

Greater than 10 % dystrophic hairs is indicative of dystrophic anagen effluvium. If the cause is not obvious from the patient’s history, toxicologic studies may be indicated. In a completed anagen effluvium in which only a few hairs remain on the scalp, all the epilated hairs are telogen bulbs (Table 2.8).

Table 2.8

Causes for dystrophic anagen effluvium

Effluvium induced by cytostatic, anticoagulant, or chemical substances, toxins (heavy metals, plant toxins), or ionizing radiation in high doses

Alopecia areata with rapid progression

Modified from Braun-Falco and Heilgemeir (1985)

In children and in persons with thin hair, the rate of dysplastic anagen can occasionally reach >50 % (Table 2.9).

Table 2.9

Causes for increase in anagen hairs devoid of hair root sheaths

Children

Loose anagen hair (>80 %, usually 90–100 % anagen hairs without hair root sheaths)

Thin hair

Androgenetic alopecia (frontal increase in % anagen hairs without hair root sheaths)

Inadequate epilation technique

In trichotillomania, 100 % of the hair bulbs are in anagen, since the patient epilates the telogen hair.

Broken-off hair may amount up to a maximum of 10 % of the total number; their prevalence is higher either when the hair is fragile or when the plucking technique was not adequate. A light microscopic hair shaft examination is indicated to exclude a hair fragility disorder.

Presence of >13 % miniature hairs is indicative of androgenetic alopecia (Table 2.10).

Table 2.10

Trichogram characteristics of androgenetic alopecia

Increase in frontal telogen rate (telogen effluvium) > 15 %

Increase in frontal anagen roots without hair root sheaths (thinning of hairs) > 20 %

Increase in frontal catagen rate > 2 %

Increase in percentage miniature hairs (terminal-to-vellus hair transformation) > 13 %

Notice: a normal trichogram does not exclude androgenetic alopecia

2.5 Laboratory Evaluation

Diagnostic tests are useful when the probability of a disease being present is neither high nor low, since high degree of clinical certainty overrides the uncertainty of the laboratory data.

The greater the number of different tests done, the greater the risk of getting false-positive or irrelevant leads. The possibilities for laboratory errors increase in the automated multiple-screen procedures. Therefore, laboratory testing must be kept sharply focused.

Clinical suspicion is the determinant, and knowledge of clinical dermatology is the prerequisite for combining medical sense with economic sense in requesting laboratory tests.

2.5.1 Biochemical Investigations

The essential biochemical investigations for hair loss depending on the patient history and clinical examination findings and the suggested biochemical ranges for achieving an optimal hair growth potential in women, resp., are summarized in Tables 2.11 and 2.12.

Table 2.11

Proposed biochemical investigations for hair loss in women

Increased hair shedding

Serum ferritin (and C-reactive protein)

Total iron binding capacity

% iron saturation

Vitamin B12

Serum and red cell folates

Free T4

Thyroid-stimulating hormone

Estradiol

Progesterone

Diffuse thinning

As above, plus hormonal investigations:

DHT

Testosterone

Prolactin

Estradiol (if menopausal)

If associated with acne or hirsutism:

Luteinizing hormone

Follicle-stimulating hormone

Androstenedione

Appropriate scans

Patterned hair loss in women

All of the above

From Rushton (1993)

Table 2.12

Suggested biochemical ranges for achieving an optimal hair growth potential in women

Variable	Optimal range	Potential problems
Serum ferritin^a (μg/L)	>40	>400
Vitamin B12 (ng/L)	300–1,000	<200, >1,500
Serum folic acid (nmol/L)	5–40	>45
Red cell folates (nmol/L)	400–1,600	>2,000
Estradiol (day 21) (pmol/L)	>300	<250 (?)
Progesterone (day 21) (nmol/L)	>30	<25 (?)

From Rushton (1993)

^aWith normal C-reactive protein level; (?) unconfirmed

In a landmark study on hormonal diagnostics in female androgenetic alopecia, Moltz investigated 125 women aged 18–68 years (mean ± SD: 34 ± 11.6) with clinically typical androgenetic alopecia. Atypical uterine bleeding, seborrhea (69.6 %), acne (42.4 %), and hirsutism (24.0 %) were frequently observed. Pathologic changes of one biochemical parameter were detected in 22.4 %, while 67.2 % revealed deviations of two or more parameters. The incidence rates of pathologic parameters were as follows (in %): ferritin = 42 %, prolactin = 34 %, estradiol (E2) = 34 %, free testosterone (fT) = 29 %, dihydrotestosterone (DHT) = 28 %, sexual hormone-binding globulin (SHBG) = 26 %, thyroid-stimulating hormone (TSH) = 20.8 %, DHEA-sulfate (DHEAS) = 19 %, testosterone = 14 %, 17α-hydroxyprogesterone = 11 %, folate = 7 %, Δ₄-androstendione = 6 %, cortisol = 6 % and vitamin B₁₂ = 5 %. Group and individual case analyses revealed significant correlations between (1) the levels of the various androgens, prolactin, and TSH and (2) the E2, sexual hormone-binding globulin and fT values; these in turn were correlated to (3) the occurrence of uterine bleeding anomalies (amount, duration, and interval) and corresponding ferritin deficiency.

In a later study aiming at biochemical and trichological characterization of diffuse alopecia in women, Rushton et al. investigated 100 women who presented with diffuse alopecia and compared them with 20 controls. In 40.9 % hormonal values were within control ranges. A raised DHT was found in 29.5 % and was the most frequently elevated androgenetic finding. 34 % had changes in iron metabolism, while in 72.0 % serum ferritin levels were below the lowest control value. Taking high doses of multivitamins can influence iron absorption. According to Rushton a raised serum folic acid (>40 nmol/L) may indicate an excessive supplement intake. Provisional indications suggest that raised folic acid and vitamin B12 levels may induce excessive telogen hair shedding. On the other hand, vitamin B12 levels are adversely affected by cyproterone acetate–estradiol (CPA–E2) therapy; therefore, patients treated with CPA–E2 may require concurrent vitamin B12 supplementation in a suggested daily oral dosage of 100–200 μg to maintain their serum concentration levels above ideally 300 ng/L. With quantitative hair data available, no correlation between hormonal levels and any hair value was established. The authors concluded that the endocrine dependence of diffuse alopecia appears to involve tissue dynamics such as receptor populations and binding protein phenomena rather than specific levels of circulating hormones. Diffuse alopecia was not associated with any major endocrine disturbance; therefore, extensive laboratory investigations would seem unnecessary in the majority of women.

However, a detailed hormonal profiling may be of value in women with marked bitemporal recession or when acne or hirsutism coexist.

Testosterone levels should be determined early in the follicular phase of the menstrual cycle (day 3–7), preferably in the morning between 8 and 10 AM. DHEAS levels can be determined at any time point. Hormonal studies should be performed when patients are off oral contraceptives.

Serum ferritin is the standard marker of iron status; however, serum ferritin is also an acute phase reactant and can be increased in inflammation.

Since high levels of serum ferritin are engendered by inflammation independently of iron stores, it is important to simultaneously determine C-reactive protein (CRP) levels.

Finally, Schmidt et al. pointed out that androgen-dependent disorders of hair growth are due to more varied hormonal disturbances than elevated androgen serum levels alone. In view of the complex hormonal interactions between androgens, thyroid hormones, and prolactin, the thyrotropin-releasing-hormone (TRH)-stimulating test was performed in 38 female patients with androgen-induced alopecia, and the results were compared with those recorded in female control persons. The test is based on feedback mechanisms between hypothalamic TRH and hypophyseal TSH and prolactin and peripheral thyroid hormones. Baseline and stimulated TSH levels were significantly elevated. Therefore, hypothyroidism was recognized to be a significant contributing factor.

In the case of prolactin, Schmidt et al. found stimulated levels also to be significantly elevated in the women with androgen-dependent alopecia. Orfanos and Hertel previously pointed out that functional hyperprolactinemia may yet be another cause of hair loss in women.

Hyperprolactinemia is the most frequent abnormality of the anterior pituitary gland. Clinical signs include inappropriate lactation, lack of menses, decreased libido, and infertility. General guidelines for diagnosing prolactin excess (hyperprolactinemia) define the upper threshold of normal prolactin at 25 μg/L for women. However, different methods for measuring prolactin are employed by different laboratories, and as such the serum reference range for prolactin is often determined by the laboratory performing the measurement. Furthermore, prolactin levels vary with age, sex, menstrual cycle stage, and pregnancy. The circumstances surrounding a given prolactin measurement (method and patient condition) must therefore be considered before the measurement can be accurately interpreted. The pathological ranges and causes for hyperprolactinemia are given in Table 2.13.

Table 2.13

Pathological ranges and causes of hyperprolactinemia

Normal	2–25 ng/mL^a
Intermediate	25–200 ng/mL^a	Lactation
		Hypothyroidism
		Drugs that block the effects of dopamine at the pituitary or deplete dopamine stores in the brain: major tranquilizers (phenothiazines), ramelteon, risperidone, trifluoperazine, haloperidol, antipsychotic medications in general, metoclopramide, domperidone, and cisapride used to treat gastroesophageal reflux and medication-induced nausea; less often alpha-methyldopa and reserpine used to control hypertension and estrogens
		Epileptic seizures
		Chronic physical and psychic stress
		Pregnancy
		Orgasm
		Breast manipulation
		High consumption of beer
Pathologic	>200 ng/mL^a	Prolactinoma (Forbes–Albright syndrome refers to galactorrhea–amenorrhea associated with a pituitary tumor)
Idiopathic conditions with hyperprolactinemia (historical eponyms)		Ahumada–del Castillo syndrome refers to the association of galactorrhea and amenorrhea
		Chiari–Frommel syndrome refers to extended postpartum galactorrhea and amenorrhea

^aThe serum concentration of prolactin can be given in mass concentration (μg/L or ng/mL), molar concentration (nmol/L or pmol/L), or in international units (typically mIU/L). Measurements that are calibrated against the current international standard can be converted into mass units using this ratio of grams to IUs; prolactin concentrations expressed in mIU/L can be converted to μg/L by dividing by 21.2

Therefore, in selected cases, evaluation of prolactin levels together with extended androgen blood levels and thyroid gland function tests should be performed to exclude underlying endocrinopathy.

Since alopecia areata is considered to be an organ-specific autoimmune disease and, at least in localized patchy disease, the clinical appearance would seem sufficient to make a diagnosis, further laboratory investigation could seem unnecessary or even inappropriate. Nevertheless, in recurrent cases or patients presenting with extensive alopecia areata, certain laboratory investigations may be indicated to detect associated autoimmune diseases and/or comorbidities that may affect the disease course (Table 2.14). An increased incidence of other autoimmune diseases, like Hashimoto’s thyroiditis and pernicious anemia, is seen among alopecia areata patients, while serum ferritin or zinc levels may have an influence on the disease course. Ultimately, the detection of antithyroid or anti-parietal cell autoantibodies may represent markers for autoimmunity in favor of the diagnosis of alopecia areata.

Table 2.14

Proposed comorbidities screening in alopecia areata

Test	Purpose
To detect associated autoimmune disorders
Antithyroid antibodies	To detect associated thyroid autoimmunity
Anti-parietal cell antibodies	To detect associated parietal cell autoimmunity
Thyroid function tests	To detect associated autoimmune thyroid disease
Vitamin B12 level	To detect associated pernicious anemia
To detect potentially disease-modifying comorbidities
CRP and ferritin level	Iron deficiency
Zinc level	Zinc deficiency
Vitamin D3 level	Vitamin D deficiency
To rule out other causes of patchy alopecia
Antinuclear antibody test	Lupus erythematosus
RPR test (or VDRL and TPPA depending on laboratory)	Syphilis II (alopecia areolaris)

The diagnosis of heavy metal toxicity requires observation of presenting symptoms, obtaining a thorough history of potential exposure (occupational, environmental, accidental), and the results of laboratory tests. Laboratory tests routinely used for seriously exposed persons include blood and urine analysis. In a study performed by Pierard, toxic metals in abnormal amount in blood and urine were observed only when >10 % of hair bulbs in the trichogram were dystrophic.

2.5.2 Microbiologic Studies

Microbiologic studies are mandatory in inflammatory conditions of the scalp with scaling, crusting, and/or pustulation.

While in children fungal infections (tinea capitis) predominate, in the adult, bacterial infection with Staph. aureus is the most prominent.

At times, repeated microbiologic studies are recommended, since with prolonged antibiotic treatments, typically in folliculitis decalvans, new and resistant pathogens may emerge, for example, gram-negative folliculitis.

Diagnosis of fungal and bacterial skin infections requires swabs and test systems for direct visualization of pathogens (KOH preparation, Gram’s stain), cultures and special tests for species identification, and the availability of the appropriate laboratory infrastructure.

2.6 Scalp Biopsy

In some cases of alopecia, a diagnosis cannot be made based on results of physical examination, diagnostic hair techniques, and laboratory studies. This is particularly the case in the scarring alopecias. In these cases, a scalp biopsy may provide the specific diagnosis. In addition, it must be kept in mind that two types of alopecia may coexist within the same patient.

In all cases of scarring alopecia, a scalp biopsy is mandatory.

By definition, scarring alopecia is characterized by a visible loss of follicular ostia due to a destruction of the hair follicle on histopathological examination. The biopsy will help to identify the cause and rule out infiltrating malignant disease.

In the noncicatricial alopecias where the follicular ostia are intact, a scalp biopsy is optional for morphometric studies on transverse sections (hair follicle density, anagen/telogen ratio, terminal/vellus hair ratio) or to detect specific findings for a particular diagnosis, such as trichomalacia in trichotillomania and the peribulbar lymphocytic infiltrate in alopecia areata.

In the inflammatory scarring alopecias with active inflammation, the type of inflammatory infiltrate (lymphocytic, neutrophilic, mixed, granulomatous), the pattern of inflammation, and its relation to the hair follicle usually enables a specific diagnosis. Where active inflammation is missing, an elastin stain will help to identify the scarring process.

Frequent problems related to the scalp biopsy are the reluctance of many dermatologists to perform a scalp biopsy and therefore lack of experience with the proper procedure and the lack of familiarity of many pathologists with scalp histopathology.

Scalp biopsies are often inadequately performed: superficial (without subcutaneous tissue), small, often tangential to the hair follicle, and with crush artifacts. Finally, the hair follicle and its derangements are complex and dynamic, while a biopsy only gives a momentary snapshot of the pathology.

Nevertheless, if done and examined properly, the scalp biopsy should be an easy, relatively painless, and bloodless procedure that represents an invaluable adjunct for confirming or establishing the diagnosis of a specific type of alopecia, whether scarring or non-scarring.

The scalp specimen obtained for histopathologic study should be large enough to include multiple hairs, deep enough to contain the hair bulb, and properly angled so that microscopic sectioning shows the entire follicular structure.

For a biopsy an area of the scalp is chosen where the disease is active; frequently the margin of the involved area shows the pathologic changes best, while areas should be avoided where there are no hair follicles present. After choosing the appropriate site, the hairs are clipped in a 1-cm² area, leaving a 2-mm stubble (Fig. 2.15a). The area is prepared with 70 % alcohol. For adequate anesthesia and hemostasis, 1.5 mL of 1.0 % lidocaine with epinephrine is injected raising a large wheal (Fig. 2.15b). To obtain an adequate vasoconstrictor effect, it is advisable to wait 20–30 min before proceeding to the biopsy. Also, areas are to be avoided that lie over the temporal or occipital arteries or in which an arterial palpation can be detected. To avoid tying long hairs in the suture material, paper tape is placed over the uncut hairs surrounding the biopsy site. An adequate biopsy specimen can be obtained by using a 6-mm punch instrument that is placed parallel to the emerging angle of the hair stubbles (Fig. 2.15c). The punch is turned through the dermis and subcutaneous fat to a level including the hair bulbs. The biopsy specimen can be grasped at the edge with a fine-toothed forceps (Fig. 2.15d), while it is cut free of attachment deep in the fat with a small, curved scissors. Alternatively, a thin 1-cm ellipse can be made, especially if the scalp is very tight or scarred, and a 6-mm punch site may not be able to be closed with sutures. The biopsy site is sutured with blue 4-0 Proline (Fig. 2.15e). Three to four stitches are usually adequate for hemostasis. The specimen is then cut in half with a # 15 blade parallel to the longitudinal axis of the hair shafts (Fig. 2.15f). One half of the specimen is submitted for the routine hematoxylin and eosin examination, while the other half for immunofluorescence studies as indicated (Fig. 2.15g). In some instances, transverse sectioning of a second, entire punch according to the Headington technique may be done for quantitative morphometric analyses of the follicles and hair.

Fig. 2.15

(a–g) Scalp biopsy

In a study of 136 scalp biopsies obtained for histopathology and direct immunofluorescence studies, we made a definitive diagnosis in 126/136. In 122/126 (97 %) the definitive diagnosis was made on the basis of histopathology alone. Characteristic direct immunofluorescence patterns showed high specificity (98 %), but low sensitivity (34 %) for lichen planopilaris and high specificity (96 %) and sensitivity (76 %) for lupus erythematosus. We concluded that the diagnostic yield of immunofluorescence studies is highest where the diagnosis of lupus erythematosus is in question.

For a discussion of the specific histopathologic conditions, the reader should consult a standard dermatopathology textbook.

2.7 Quantifying Hair Loss

Reliably assessing the actual shedding of hair is a crucial diagnostic point in trichological practice. To fulfill office requirements, the test should be easy, noninvasive, and not time-consuming. Many methods have been proposed, but all need standardization. The hair pull represents a poorly sensitive method, while telogen percentage in the trichogram does not correlate with severity of hair loss.

2.7.1 Daily Hair Counts and Hair Wash Test

Daily hair counts are done by the patient at home to provide a quasi-quantitative assessment of the number of hairs shed daily. For this purpose, the patient is instructed to collect all hairs that fall out during the morning grooming, including hairs on the pillow, sink, comb, brush, and shoulders as well as all hairs that come out with the morning shampoo. Placing a piece of nylon netting or gauze over the drain will help secure hairs otherwise lost during washing. The entire morning’s collection is placed in a clear, smooth, plastic bag. The date and information on whether the hair has been shampooed or not is written on a label placed on the bag (Fig. 2.16). The patient is also asked to count every hair in the bag and to record the total count on the label as well. Typically, hair collection should be done for 14 consecutive days, and all 14 bags are brought to the physician’s office.

Fig. 2.16

Daily hair count

It is more practical to ask patients to collect and count the hairs on the 5–7 days prior to the trichogram (daily hair counts) and after washing the hair following the trichogram (hair wash test).

The amount of normal hair shed may vary from 35 to 180 hairs, depending on the amount of scalp hair and seasonal factors. The number is usually higher on the day of shampoo, especially when the hair is not shampooed daily.

In diffuse telogen effluvium and anagen effluvium, the number of hairs shed daily is in the 100s, while in androgenetic alopecia it may well be less than 100.

Therefore, it is not wise to trust in rules of thumb, such as a daily hair count of up to 100 is normal, when evaluating hair loss in women.

While the daily hair count is a cumbersome procedure, it has been proposed that the wash test is probably the best method to adopt. In the wash test, the patient, 5 days after the last shampoo, washes the hair in the sink with its drain covered by gauze. The hairs entrapped in the gauze are then counted. In one study assessing hair shedding in children, the wash test proved to be reliable, with a cutoff point of normality close to 11. Wash test values increase with age. Age-dependent normal values in adults do not exist.

2.7.2 Office-Based Computer-Assisted Image Analysis

Eventually, measurement of the effects of treatment needs to be quantified reliably. The method should be more sensitive than the wash test and capable of analyzing relevant parameters of hair growth, which are hair density, hair diameter, hair growth rate, and anagen/telogen ratio.

For this purpose, computer-assisted image analysis has been proposed: Some patents have been filed and publications followed since the 1980s. However, it soon became clear that hair is a tricky material for automated computer-assisted image analysis and that numbers might not all be considered as reflecting hair measurements. Physical properties of hair, that is, the object and the variability of the skin, and their background are very complex. The multilayered fiber is composed of a nonpigmented cuticle, a cortex with presence or absence of pigment granules, and a medulla filled with proteinaceous material or air cavities. On top, its organization and orientation at the exit point from the skin must also be taken into account. A follicular unit comprising a number of hair follicles (occasionally up to 5) may exit from a single orifice at the skin surface, and it may be difficult to count individual hair fibers. Some attempts have suggested that use of fully automatic systems may be an option, but this has not been made available to the public.

A software named TrichoScan combining epiluminiscence microscopy with digital image analysis has been proposed and marketed for automated image analysis of scalp hair. This method requires the use of hair dyes for improved detection of less pigmented and thinner hair. Advocates for the method declare that a system must be able to analyze the biological parameters that constitute hair growth, which are (1) hair density (n/cm²), (2) hair diameter (μm), (3) hair growth rate (mm/day), and (4) anagen/telogen ratio. Intra-class correlation of approximately 91 % within the same operator and an inter-class correlation of approximately 97 % for different operators suggested that the method was very precise and reproducible.

Using standardized photographic equipment and calibrated processing for contrast-enhanced phototrichogram (CEPTG) analysis, van Neste established a protocol that was equally sensitive as scalp biopsies for hair detection and growth staging. Taking this as a reference method, we performed a study to evaluate the advantages and limits of TrichoScan for human hair growth analysis. The study was prompted by a number of variations that were unexpected after considering the original claims for accuracy promoting the TrichoScan method for hair growth measurement. Our investigation did not corroborate these claims. With the available software, numbers were displayed for hair counts (all fibers detected by the software in the target area and those that touched the border of the target area). This number is also split into resting hair (telogen) and those considered growing, that is, in anagen phase of the hair growth cycle. The commercially available software provided to dermatologists and hair clinics for office based use originally did not display the thickness of hair fibers and the hair growth rate. Although cumulative thickness may be an indirect way to approach the hair thickness measurement, it provides a global measure that depends on hair cycle duration. Also, we challenged that TrichoScan measures growth accurately. First, there are no growth rates on the data display. Second, the precision of anagen hair detection is not optimal. Indeed, the anagen percentage was underestimated (difference > 5 %) in two out of four scalp sites as well as in the beard area, but it was overestimated when thinning was more important (overestimation of 32 % anagen hair proportion in the vertex). A number of these errors (especially with thin hair detection) have been described by others using the TrichoScan method in normal scalp sites, especially a density that was underestimated by 22 % and the lack of detection of thinner hair. As thinning is a phenomenon associated with androgenetic alopecia, published documents and our experimental study clearly documented that especially thin hair counts, as well as growth staging generated by the TrichoScan method, may not be considered as reliable. Therefore, we concluded that TrichoScan in the present form would not qualify as a test method for quantification of hair loss according to our internal and other standards particularly in patients with androgenetic alopecia.

Computerized methods require further optimization. Ease of use and fast image processing, as pointed out by others, are certainly appreciated. Nevertheless, albeit speed is considered smart in our culture, we believe that customers, that is, clinicians, patients, and pharmaceutical or cosmetic companies, deserve the highest standard and a better service than merely a fast one. All should be given the best possible and clinically most relevant information about hair measurements – both qualitatively and quantitatively – that have diagnostic, prognostic, and therapeutic relevance.

2.8 Hair Database Sheet

The patient and family history, history of hair cosmetic procedures, clinical examination findings (of hair loss pattern and scalp condition), diagnostic techniques, laboratory data, and results from microbiological studies and scalp biopsy, as indicated in the individual case, enable a definitive diagnosis to be made. For documentation purposes and facilitation of interpretation, findings are recorded on a hair database sheet (Fig. 2.17).

Fig. 2.17

Hair database sheet

Suggested Reading

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Patient History

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Trachsler S, Trüeb RM (2005) Value of direct immunofluorescence for differential diagnosis of cicatricial alopecia. Dermatology 211:98–102CrossRef

Quantifying Hair Loss

Guarrera M, Semino MT, Rebora A (1997) Quantitating hair loss in women: a critical approach. Dermatology 1997:12–16CrossRef

Hoffmann R (2001) TrichoScan: combining epiluminiscence microscopy with digital image analysis for the measurement of hair growth in vivo. Eur J Dermatol 11:362–368

Ihm CW, Lee JY (1991) Evaluation in daily hair counts. Dermatologica 182:67CrossRef

Olsen EA (1993) Clinical tools for assessing hair loss. In: Olsen EA (ed) Disorders of hair growth: diagnosis and treatment. McGraw-Hill, New York, pp 59–69

Rampini P, Guarrera M, Rampini E, Rebora A (1999) Assessing hair shedding in children. Dermatology 199:256–257CrossRef

Seung Ho Lee, Oh Sang Kwon, Jun Gyu Oh et al (2004) Phototrichogram: Evaluation of Modified Methods with Bleaching and Trichoscan. Poster presentation at the European Hair Research Society, Seoul, 2004

Van Neste D, Trüeb RM (2006) Critical study of hair growth analysis with computer-assisted methods. J Eur Acad Dermatol Venereol 20:578–583CrossRef

Hair Database Sheet

Caserio RJ (1987) Diagnostic techniques for hair disorders part III: clinical hair manipulations and clinical findings. Cutis 40:442–448

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