Stress Hair Loss - Clinical Approach 

    
​ It is most important for successful patient management and treatment to make the correct diagnoses. The following five steps  are key to making the right diagnosis, to proper treatment, and to patient satisfaction:
1.Listen 
2.Look 
3.Touch 
4.Magnify 
5.Sample 

Many etiological factors can lead to clinical hair loss, including genetic predisposition, systemic illness, drugs, endocrine abnormalities, psychological distress, diet, trauma, infections, autoimmunity, and structural hair defects. Hair is one of the fastest growing tissues of the body; therefore, any metabolic and hormonal changes can result in shedding and alopecia. Because of the multiplicity of causes that can result in hair loss, a thorough history is of critical importance in developing the initial differential diagnosis.

Listen
The first task of a physician is to address the patient's concerns fully, exploring the impact of alopecia on the patient's psychosocial well-being. A simple questionnaire can help lead the conversation and can give first hints to possible underlying causes (Figure 1.9). Important questions are as follows: When did you begin losing your hair? Are you shedding a lot of hair and do you find hair all over the place, or did you notice a
more gradual thinning? Where are you losing your hair? How many hairs are you approximately losing per day? What percentage of your hair have you lost in what amount of time?

Moderate and massive shedding is frequently seen in telogen effluvium and alopecia areata. Gradual thinning can be seen in androgenetic alopecia and often in cicatricial alopecias. The pattern described by the patient can also give first hints. Patches of hair loss are
suspicious for alopecia areata and cicatricial alopecia, generalized shedding is seen in telogen effluvium and sometimes alopecia areata, and frontoparietal or vertex thinning is most commonly seen in androgenetic alopecia. Further questions should comprise present and past physical and mental health conditions and a full list of current and past medication. How is your general health? Have you had any severe diseases in the past? Are you or have you been taking any medication? Do you have any thyroid problems? What happened in your life 3–6
months prior to the onset of your hair loss (pregnancy, high fever, operations/general anesthesia, crash diets, accidents/trauma, or psychological stress)?

Patient approach.
It is also important to ask about the diet in general (well balanced/vegetarian, vegan or pescetarian), family history of hair loss, and hair care practices. Unbalanced and restrictive diets or strict vegetarian or vegan diets can implicate iron deficiency or other deficiencies (zinc,
selenium, vitamin B12, etc.). A positive family history of alopecia areata or androgenetic alopecia may point to a genetic predisposition for hair loss. Some hair care practices (e.g., bleaching, back combing, permanent waving, hot combs, hot blow drying, and straightening) may result in structural defects and hair breakage. Furthermore, heavy extensions, dreadlocks, cornrows, tight ponytails, and braids can lead to traction alopecia.

Questions should also be asked about the loss of axillary and pubic hair, eyelashes, eyebrows, and other body hairs, as any hair-bearing area may be affected by alopecia areata or trichotillomania. Female patients should be asked about the regularity of their menstrual cycle; intake, duration, and change of oral contraceptives; use of other hormonal contraceptives; and/ or onset of menopause. It is also important to know if a
woman already has children or has recently given birth or if there is an unfulfilled desire to have children. Excessive growth of body hair, irregularity in menstrual cycle, and unwanted childlessness are often indicators of hormonal imbalance. These patients need a thorough
endocrinological workup with a gynecologist and/or endocrinologist.

The age of the patient is also very important to make the first differential diagnosis. Certain conditions are more common in childhood compared to adulthood. The two most common forms of hair loss in children are tinea capitis and alopecia areata.

Finally, the physician should ask if the patient has tried any treatments for hair loss. The patients will often answer this question by stating that they have already tried everything. Because most medications for hair loss take at least 3 to 4 months to start working, it is crucial to exactly find out what the patient had been taking, how regularly, and for how long. It is also important to know if the patient noticed any effects or side effects from the treatment.

The patient's expectations should be acknowledged and fully explored. Many patients with hair and scalp problems become frustrated when their worries are either ignored or dismissed as insignificant. Explanation and discussion will oftentimes relieve the distress or may even resolve the problem without specific intervention.

Occasionally, an underlying depression or dysmorphophobia (pathologically focused fixation on body image) may be present. It is important that these psychological and psychiatric conditions are recognized and carefully addressed and if possible discussed with the patient. Body dysmorphophobic patients are a challenge for every physician. These patients will often question diagnosis, treatment, and treatment results. This can be frustrating for the treating physician. Nonetheless, it is very important to take the patient's concerns seriously, confront the patient with the problem, and carefully lead the patient to an appropriate psychological or psychiatric treatment.

Look and touch
A thorough inspection of the entire scalp is the first step of the clinical examination. The clinical examination should be performed in three steps. First, examine the pattern of density and distribution of hair. Certain patterns are characteristic for certain diseases. Bald patches are seen in alopecia areata and cicatricial alopecia.

Second, inspect for scales and erythema. It is important to determine if the hair loss is associated with signs of inflammation or scarring.
Scarring can be caused by trauma or can lead to the diagnosis of primary or secondary cicatricial alopecias. Scaling and dandruff can also be part of cicatricial alopecias or can point to a concomitant scalp disorder like psoriasis, seborrheic dermatitis, or pityriasis amiantacea.
Third, use simple methods to determine the activity of hair loss and regrowth.

Pull test
A pull test should be conducted in every hair patient on different areas of the scalp. The patient should always be informed about the test and about the fact that any pulled hair would fall out anyway during that day. Approximately 60 hairs are grasped between the thumb and index and middle fingers from the base of the hair near the scalp and firmly, but not too forcefully, tugged away from the scalp. If more than 5%–10% or three to six hairs are pulled away from the scalp, this constitutes a positive pull test and indicates active hair shedding. Less than three hairs are considered normal physiological shedding. The patient must not shampoo at least 1 day prior to the pull test. The pull test helps to determine the localization and severity of hair loss.

Contrast paper
The contrast paper method should be part of every hair examination. A contrast paper (white in patients with dark hair and black in patients with light or white hair) is simply placed vertically against the hair near the scalp. The amount of regrowing hair (tapered tips) and hair breakage (blunt tips) can be easily detected.

Pull test: (a) approximately 60 hairs are grasped from the proximal portion of the hair shafts at the level of the scalp. The hairs are then tugged from proximal to distal end. (b) The number of hairs extracted is counted. It is normal to pull up to 6/60 (<10%) hairs. More than 6/60
hairs indicates a positive pull test and implies pathology. This is a 57-year-old female with diffuse alopecia areata displaying a positive pull test.

Hair counts
It is normal to lose 100–150 hairs per day. Daily scalp hair counts can sometimes be useful to the physician to help quantify how much the patient is losing. The patient is asked to collect all the hairs shed in 1 day, count them, and place them in plastic sandwich bags. All hairs shed in
the shower, sink or brush, counter, or pillow are collected. Shampoo days are labeled separately. The patient is instructed to do this for 7 days. If the patient is losing less than 100 hairs per day, it can be suspected that there is no active shedding. However, the physiological loss of 100–
150 hairs per day is only an approximate value. It is impossible for the physician to know how much hair the patient was shedding prior to the onset of the hair problem. Performing a hair count is tedious and time consuming for the patient, but it is something that the patients can do on their own to follow their progress. A hair count should be reserved for exceptional cases, because it can also trigger fears about the hair loss and
aggravate a fixation on the hair problem.

A contrast paper positioned at an involved area of the scalp will help determine the length, size, and overall caliber of the hair shafts. This alopecia areata patient showed 1 month of spontaneous regrowth in a bald patch without any treatment.

Bag sign
Sometimes, patients present with a bag of hair to show the physician how much they have lost. This so-called bag sign frequently points to the diagnosis of telogen effluvium. It is important to closely look at the hair and the roots to determine if the hairs are telogen hairs and to
ask the patient over how many days the hair has been collected .

Global photography
Global photography is an essential tool in the everyday hair clinic. It easily allows the physician as well as the patient to assess scalp coverage in general and certain areas of thinning or bald spots.

Standardized or semistandardized scalp pictures should be taken of every hair patient at their first visit or before the start of a new therapy. Disease progression or success of therapy can be tracked when photographs are taken at a later time point.

Magnify
The second step of the clinical examination should involve magnifying devices for a better detection of the presence or absence of follicular ostia; the evaluation of signs of inflammation; and the assessment of hair thickness, hair density, and differences in hair caliber.

Dermoscopy
A dermatoscope is used in every dermatological skin examination for the examination of different skin lesions and early detection of melanoma and nonmelanoma skin cancer. Traditional dermatoscopes consist of a magnifier (typically 10-fold), a nonpolarized light source, a transparent plate, and a liquid medium between the instrument and the skin. This allows inspection of skin lesions unobstructed by skin surface reflections. Modern dermatoscopes dispense with the use of the liquid medium and instead use polarized light to cancel out skin surface reflections. A dermatoscope with polarized light should preferably be used for the examination of the scalp, as the liquid medium of the traditional dermatoscope leaves an oily film on the scalp.


Videodermoscopy
When dermatoscopic images or videos are digitally captured or processed, the instrument can be referred to as a “videodermatoscope.” In the past years, this noninvasive technique has revealed novel features of scalp and hair disorders and has become more and more
popular for clinical and research use.

A videomicroscope can be equipped with various objective lenses. The usual working magnifications are 20-fold to 100-fold. All digital images may be stored for further controls. Several reports have shown the usefulness of this technique in diagnosing hair and scalp disorders, such as microsporiasis, androgenic alopecia, alopecia areata, lipedematous alopecia, pediculosis, or inherited hair shaft abnormalities.

Videodermoscopy in combination with analyzing software allows the determination of hair density and thickness without the need to remove hair for diagnostic purposes. The measurement of thickness and density at the first visit or before the start of a new treatment and at a later time point allows one to track disease progression and therapy success. It can be used in a semistandardized way, by marking an area on the scalp,
for example, 12 cm from the glabella to the frontal scalp. The same area can then be measured again at subsequent visits.

Videodermoscopy also allows in vivo visualization of the epidermal portion of hair follicles and perifollicularepidermis. It is useful for the differential diagnosis between cicatricial alopecia and noncicatricial alopecia by visualizing follicular ostia and between alopecia areata (yellow dots) and trichotillomania (broken hairs at different distances from the scalp). In addition, one may study the vascular pattern of the scalp [30].
Dermoscopy and videodermoscopy of hair and scalp are also referred to as trichoscopy.

Phototrichogram
The phototrichogram is a noninvasive method for followup diagnostic of hair growth parameters. first described this macrophotographic technique for longterm observation of hair growth on different body sites. The term phototrichogram was first used by Bouhanna et al.. Phototrichograms are mainly used for the evaluation of scalp hair.

The basic principle of the phototrichogram is taking close-up photographs of a certain defined scalp area. Before taking the first photograph, the hair in the area is cut close or short to a defined length (usually 1 mm). To increase the contrast of hair and scalp, the hair has to be dyed with dark hair dye to make vellus hair and light or white hair visible against the background. After certain periods, repeated photographs are taken. Different image analysis techniques allow the determination of hair growth rates, anagen to telogen ratio, scalp coverage, hair density, and vellus to terminal hair ratio.
Several variants of phototrichograms have become popular for evaluating hair in the clinic and in clinical research trials. Modern techniques use automated digital image analysis 

Depending on the type of image analysis, the following parameters can be determined:
1.Total number of hairs per area (hairs/cm2)
2.Vellus to terminal hair ratio
3.Anagen to telogen ratio
4.Linear hair growth rate (millimeters per day) (measured by the change in length of renewable hair
on the subsequent picture)
5.Hair thickness

The phototrichogram, especially when combined with automated digital image analysis, is a reliable, reproducible, noninvasive technique. It can be used to support the diagnosis. Early changes in androgenetic alopecia can be detected well. It can also be used to track disease progression and success of therapy and is therefore frequently used in clinical trials.

However, most hair patients are concerned about the clipped, bald area on the scalp. Automated techniques are usually not suitable for dark skin types because of the lack of contrast. Patients with allergies to hair dye are excluded from this technique.

Sample
If the diagnosis is in doubt or the physician finds signs of inflammation and scarring, it becomes necessary to take hair and/or skin samples.

Light-microscopic examination
Hairs extracted by slow pull can be examined under a light microscope. Hair shafts are mounted in parallel between two glass slides taped together. A drop of cyanoacrylate glue placed on the slide will give greater contrast under the microscope compared to dry mount. Roots should be examined to determine the stage of the hair cycle and for the presence of dystrophy. Hair shaft abnormalities (which can increase hair fragility and cause hair loss) can be diagnosed with this method. The hair shafts need to be examined to detect fractures, irregularities in coiling and twisting, and extraneous matter. The free ends of the hair should be checked to see whether they are tapered, cut, fractured, or weathered. If fungal diseases are suspected, hairs should be placed on a glass slide with 20% potassium hydroxide added to demonstrate fungal spores and hyphae.

Trichogram
A trichogram is the traditional method for the morphological, microscopic examination of hair roots. It was first developed by van Scott in 1957 , and the
term “trichogram” was first used by Pecoraro in 1964 In general, the technique involves the examination of two different scalp areas. If androgenetic alopecia or telogen effluvium is the tentative diagnosis, hair is plugged from the frontoparietal and occipital scalp. If
alopecia areata of traction alopecia is suspected, the hair is plugged from an active area and an inactive area . The hair should not be washed and should only be combed gently 5 days prior to epilation to avoid premature plugging of telogen hairs. Using a rubber-coated medical clamp, 50–70 hairs are plucked at two specific scalp locations depending on the hair disorder. The instrument is closed tightly over the
hairs close to the scalp surface. Then, the hairs are plugged with one quick, forceful pull in the direction of hair growth. For optimal evaluation results, hair bulbs are immediately embedded with their roots on a glass slide in an embedding medium, which allows microscopic
evaluation later. If mounted on a glass slide in water or on adhesive tape, the trichogram must be examined
immediately by microscopy. The microscopic evaluation is done by low-power microscopy (not more than 40-fold
magnification). The following types of hair roots can be distinguished:
Normal anagen hair
Dysplastic hair (anagen hair without a root sheath)
Catagen hair
Telogen hair
Dystrophic hair (hair with a tapered proximal end
instead of a real root)
Broken hair (with a sharp horizontal proximal end)


Normal values for adult scalp hair are >80% for anagen hair, <20% for telogen hair, <5% for dystrophic hair, <3% for catagen hair, and <10% for broken hair. An increase in dysplastic hair can be found in children with loose anagen syndrome and when the hair is plugged
too slowly. An increase in telogen hair in both the frontoparietal and occipital areas is found in an active diffuse telogen effluvium. If the increase of telogen hair is higher in the frontoparietal area in combination with variation in hair shaft diameter, androgenetic alopecia can be suspected. An increase in dystrophic hair may indicate a stronger toxic agent such as thallium, cytotoxic drugs, or high doses of vitamin A-acid, or can be found in active alopecia areata.

Unit Area Trichogram
The unit area trichogram is an advanced trichogram technique that was developed mainly for clinical trials. The unit area trichogram is based on plucking hair in a defined area (usually >30 mm2) and allows the determination of hair density.
Because anagen to telogen ratio, hair density, and thickness can be easily determined by videodermoscopy and phototrichogram, trichograms should be reserved for special cases like loose anagen syndrome or diffuse alopecia areata. The hair plucking causes discomfort to
the patient and leaves a small bald patch that can last for weeks. Moreover, many patients find it unpleasant not to shampoo for 5 days.

The trichogram/pluck test is another method of assessing hair loss. On the fifth day after the last shampoo, hairs are taken from specified sites. (a) The surrounding hair is fixed with clips, and 60–80 hairs are grasped with a hemostat covered with rubber and plucked, twisting and
lifting the hair shafts rapidly in the direction of emergence from the scalp. (b) Anagen hairs are distinguished from telogen hairs, and anagen to telogen ratios are calculated.

​Biopsy
A scalp biopsy is the ultimate tool for diagnosis of hair and scalp disorders. Scalp biopsies are indicated in all cases of cicatrizing alopecias and in all cases of unexplained non-cicatrizing alopecias. It involves, following local anesthesia, removal of one or two small 4- mm punches down to the level of subcutaneous fat to remove the entire follicular unit; the skin is subsequently sutured. Horizontally cut punches can be
examined for number of hair follicles, follicular units, hair diameter, integrity of sebaceous glands, and growth parameters (terminal to vellus hair ratio, anagen to telogen ratio, and catagen hair). A punch biopsy can be trisected at two levels, and subsequently horizontal sections are read from the base of the follicle to the papillary dermis.

Normally, a 4-mm punch of the scalp has 35–40 hairs at the upper level in the papillary dermis. At the level of the reticular dermis near the base of the infundibulum, the number is reduced to 35; at deeper levels near subcutaneous fat, the numbers are even lower, at around
30. The upper levels contain telogen and anagen terminal hair, as well as vellus and vellus-like miniaturized hairs. The mid-level consists of telogen and anagen terminal hairs. The deeper levels contain anagen terminal hair, as only the roots of thick anagen follicles reach down to the
subcutaneous fat. The difference between the upper levels and the mid-levels is usually the number of vellus or vellus-like hairs. The difference between the mid-levels and the lower levels is the number of terminal telogen hairs. Anagen to telogen hair ratios as well as terminal to vellus ratios and the total number of hairs per square centimeter can easily be calculated on the bases of the aforementioned factors and the morphology of the follicles. The presence, type, and localization (peri-, intra, or interfollicular) of inflammatory cells can also be
detected at all levels of the biopsy.

For cicatrizing alopecias, the following recommendations were developed at a consensus meeting in February 2001: One 4-mm punch biopsy including subcutaneous tissue should be taken from a clinically active area, processed for horizontal sections, and stained with hematoxylin and eosin. Elastin (acid alcoholic orcein), mucin, and PAS stains may provide additional diagnosis-defining information. A second 4-mm punch biopsy from a clinically active disease-affected area should be cut vertically into two equal pieces. One half provides tissue for transversely cut routine histological sections, and the other half can be used for direct immunofluorescence studies. 


How to perform a scalp biopsy. (a) To obtain sufficient histopathologic information, the scalp biopsy should be taken from an active inflammatory area containing hair follicles or active hair destruction. In noninflammatory conditions, a biopsy in a representative area is sufficient.
If possible, the biopsy should be taken from a cosmetically less-apparent area of the scalp. Staying away from hair parts or the frontal portion of the scalp is recommended. The area to be biopsied is marked with a red China marker. For local anesthesia, lidocaine 1% with epinephrine in a concentration of 1:100,000 is injected with a 30-gauge needle into the scalp. Epinephrine causes vasoconstriction, which has a hemostatic effect in a highly vascular site such as the scalp. In addition, a mandatory waiting period of at least 10 minutes is suggested following the anesthetic injection. This allows the vasoconstrictive effect of epinephrine to take effect and maximize the hemostasis. (b) A 4.0-mm punch biopsy is placed parallel to follow the direction of the hair. In patients who have curly hair as in the figure, insert the punch perpendicular to the scalp. (c) Direct vertical pressure is applied along with the rotation of the punch.

Penetration of the punch to a depth of approximately 3.5– 4.0 mm is sufficient to obtain a full scalp thickness. The typical punch should be pushed right through to the hub. (d) The same needle for the anesthesia can be used to hook the tissue beneath the hair bulbs. (e) Aluminum chloride 20% solution on a Q-tip can be used for hemostasis after the biopsy has been removed. (f) The biopsy defect is closed with a blue-colored monofilament suture, which helps to identify the suture on the hairy scalp, particularly with pigmented hairs. The suture needle is passed through the upper dermis, preventing damage to the hair bulbs located in the deep dermis.

Wound dressings are not necessary for the scalp. Biopsies are an excellent tool for the diagnosis of hair and scalp disorders, but they are difficult to reproduce because the one area of interest has been removed; therefore, they are less suitable for the
evaluation of therapy success and disease progression.

However, in cicatricial alopecia, subsequent biopsies may be useful to document burnt out stages. A scalp biopsy is
an invasive technique and results in discomfort for the patient and leaves a small scar. The horizontal preparation
and evaluation of the punch biopsy requires an experienced pathology technician and dermatopathologist.

Laboratory tests
Laboratory tests should be performed in every patient with hair loss. Every patient should be checked for iron deficiency and thyroid dysfunction. Especially in patients with telogen effluvium, it is important to find out underlying causes. Low serum ferritin levels (<70 ng/mL)
can indicate a lack of iron storage and can be the cause or aggravating factor for hair loss. Thyroid dysfunctions are often seen in patients with telogen effluvium, most frequently hypothyroidism; slight fatigue and mild depression are often the only symptoms along with hair
loss. Hashimoto thyroiditis is often accompanied by alopecia areata. A thyroid-stimulating hormone level should be investigated. Vitamin D deficiency can also be associated with hair loss. Furthermore, the patient can be checked for low vitamin B12, selenium, and zinc levels as
aggravating factors.