Telogen effluvium

 

Salient features

• Increased shedding of otherwise normal telogen club hairs in response to a pathologic or normal physiologic change in health status
• Telogen effluvium is the most common cause of diffuse hair loss.
• Telogen effluvium is subdivided into acute telogen effluvium, chronic diffuse telogen hair loss, and chronic telogen effluvium.
• Differential diagnoses include alopecia areata incognita and psychogenic pseudoeffluvium.
• Spontaneous recovery can be expected once a cause is identified and eliminated

 

    

Introduction

The second most common cause of hair loss in women after FPHL is TE. The latter presents as a nonpatterned increase in shedding of terminal hairs, diffusely over the entire scalp, and can produce an apparent thinning of hair in severe cases. While both genders can experience TE, attitudes toward hair loss result in a greater proportion of females who complain.

The term TE was first coined by Kligman to describe increased shedding of normal club hairs, with the hypothesis that irrespective of the cause, the follicle tends to behave in a similar fashion by undergoing a premature termination of anagen, precipitating telogen.

TE is best characterized by a premature termination of the anagen (growing) phase of hair follicles, with a resultant increase in telogen (resting) phase hairs leading to excessive and diffuse loss of club hairs. Typically, TE is self-limiting, and full recovery can be expected once the specific causes are identified and corrected.

The hair cycle

In the normal scalp, there are ~100 000 hair follicles of which ~90% will be in the anagen phase, and the remaining 10% in telogen. Telogen typically lasts for three months. Daily, ~50–200 hairs undergo exogen and are shed. Only 500–1000 follicles are in the transitional catagen phase on any given day. The biologic clock that determines the end of the anagen phase and the beginning of the catagen/telogen phase is a complex phenomenon.

 

During the anagen phase, each human hair will grow for a few months to years before it becomes a telogen hair and is shed. Scalp hair grows longer than hair on other parts of the body because its anagen phase is longer. Various metabolic alterations such as pregnancy, malnutrition, and other stresses are capable of adjusting the biologic clock within hair follicles, and it is possible for abnormally large numbers of hairs to enter the telogen phase simultaneously. When this happens, the hair loss is termed a telogen effluvium.

 

 

An average scalp

 

 

Clinical features

 

Depending on the clinical course and symptoms, TE can be subdivided into 3 subgroups: classic acute TE, chronic diffuse telogen hair loss, and chronic telogen effluvium. Irrespective of clinical subtypes, the most representative manifestation of TE is diffuse excessive shedding of club hairs. Thinning of the hair involves the entire scalp and may also be noted on other hairy regions of the body (e.g. pubic and axillary hair).

 

 

The typical patient of Telogen effluvium 

·       The typical patient is a woman claiming to have always had a "full head of hair" and reporting her hair to come out suddenly "by the handful". 

·       Usually, she is accurate about the date of onset of her shedding. 

·       She is in good health, without signs of anorexia or nutrient deficiencies. 

·       She admits to having been in an anxious state for some months, and felt, occasionally or not, a painful or burning sensation at the scalp (trichodynia).

·       Usually, the course of the disorder is chronic but intermittent, with apparent remissions being irregularly intermitted by relapses.

·       The shed hairs do not exhibit telogen roots, but mostly exogen ones.

·       This distinct entity, shares some analogies with alopecia areata, including the triggering role of emotional stress, trichodynia and the frequent association with Hashimoto's thyroiditis.

 

Acute TE

This is the most classic type of TE originally described by Kligman in 1961. Typically, acute and diffuse hair shedding is noted approximately 3 months from causative events, since it takes that amount of time for a hair follicle to progress through the telogen phase and then finally be shed. There is neither clinical nor histologic evidence of inflammation on the scalp. Usually shed hair demonstrates the morphology of club hairs in the late stage of telogen without an enclosing sac (root sheath cells) and pigmentation. Anagen hairs are prematurely shifted into telogen hairs. The normal anagen/telogen ratio is 90:10. In TE, the ratio shits to 70 % anagen and 30% telogen, with daily shedding up to 300 telogen hairs. Women often present with the “bag sign”: bringing in bags with hair that they have collected every day or over a couple of days. The global examination of the scalp may show a reduction in hair density especially in the temporal area. The pull test is usually positive. Usually gradual decrease and termination of hair shedding and the regrowth of new anagen hairs can be expected by 3-6 months.

 

Chronic diffuse telogen hair loss (CDTHL)

A temporary insult usually triggers sudden- onset diffuse hair shedding as seen in acute TE, which recovers after the elimination of triggering stress. However, telogen hair shedding may last longer than 6 months. Chronic diffuse telogen hair loss (CDTHL) is one such condition that is secondary to various causes as mentioned in the table. The relation between CDTHL and the causative factors needs to be reversible and reproducible.

 

Chronic Telogen Effluvium (CTE)

CTE is an idiopathic distinct entity characterized by an excessive alarming diffuse shedding of club hairs in women between the ages of 30 and 60 years, with a prolonged fluctuating course and near normal histology. Telogen hair shedding extends more than 6 months to several years duration. The exact pathogenesis of CTE is not known, but it is theorized that it is due to reduction in the duration of anagen growth phase without miniaturization of hair follicles. Also, the etiology of CTE is unclear and it is diagnosed after excluding other cause of chronic diffuse hair loss.

 

Diagnostic feature of CTE:

·       History of abrupt, excessive, alarming, diffuse, generalized shedding of hair from a normal looking head is the main feature of CTE.

·       The patient may claim that the shed hairs block the drain after showering or bring a sack of shed hair to convince excessive hair loss.

·       Obvious diffuse thinning is not a feature of CTE, though many of these women do notice 50% reduction in the volume of their pony tail thickness

·       Marked bitemporal recession of hairs is frequently observed.

·       A positive hair pull test at all sites of scalp (vertex, occiput and sides) is seen in active phase.

·       Absence of central parting and miniaturization of hair.

·       Absence of any cause of chronic diffuse hair loss.

·       Counting of total number of telogen hairs and vellus hairs shed during standardized shampooing (wash test) has been reported as a good tool to differentiate between CTE and FPHL.

·       Ten percent or more of vellus hairs is considered enough to diagnose FPHL.

·       Normal histological feature except for a slight increase in the telogen hair follicles.

 

 

Etiology

Clinical subtypes and potential etiology of TE

Acute TE

 

·       Shedding of the newborn (physiologic)

 

·       Post febrile (extremely high fevers, e.g. malaria)

 

·       Postsurgical (implies major surgical procedure)

 

·       Postpartum (physiologic)

 

·       Weight loss/ Crash diets

·       Drugs(may cause CDTHL)

 

Chronic diffuse telogen hair loss

 

·       Hypothyroidism

·       Aging

·       Malnutrition (protein calorie malnutrition)

·       Iron deficiency (controversial)

·       Zinc deficiency (severe cases)

·       Severe chronic illness

·       Severe, prolonged psychological stress (controversial)

·       STD (HIV infection and syphilis)

Chronic Telogen Effluvium

Idiopathic

 

In the normal human scalp, the number of total hair follicles and the ratio between anagen and telogen hair are maintain as constant. On average, telogen hair accounts for around 10% of scalp hairs. Any factors that affect the duration of each phase of hair cycles with resultant abnormal increase of club hairs loss can be potential TE triggers.

 

PREGNANCY

Telogen gravidarum is probably the most widely recognized form of classic TE. The hair loss that commonly occurs following pregnancy is generally seen 2 or 3 months postpartum, there is progressive increase in anagen hairs during pregnancy. As a result there is delayed transition from anagen to catagen/telogen, which results in a simultaneous shedding of large numbers of terminal hairs during postpartum. This hair does eventually regrow; however, the returning hair may show changes in texture, color and curliness, and may not attain its previous length. As such, pregnancy (parturition or abortion) may in some cases produce permanent changes in anagen length.

 

THYROID DISEASE

Association between hypothyroidism and TE has been well established. The manifestation is more likely to be CDTHL rather than acute TE. Hair regrowth can be observed around 8 weeks after the initiation of thyroid hormone replacement in patients with hypothyroidism.

AGING

Diffuse hair loss in the scalp and body can be seen in elderly persons with histopathology increase in telogen ratio.

 

WEIGHT LOSS (CRASH DIET)

A vigorous weight loss more than 10 kg within 3 weeks to 3 months can result in remarkable increase in telogen counts (25% to 50%) and lead to acute TE.

 

ZINC DEFICIENCY

AE is an autosomal recessive disorder characterized by zinc malabsorption with resultant hair loss, acral and periorificial dermatitis, diarrhea, immunodeficiency, mental and neurological disturbances, and growth retardation. CDTHL is a typical pathophysiology for hair loss. Supplemental zinc should improve all symptoms, including hair loss.

Acquired zinc deficiency resembling AE may develop in parenteral alimentation, GI tract surgery, pancreatitis, IBD, or AIDS nephropathy as well as in premature infants and cause acute TE or CDTHL.

 

SYSTEMIC DISEASES

Lymph proliferative disease, advance malignancy, collagen disease (SLE, DM), hepatic disease, chronic renal failure, systemic amyloidosis and inflammatory bowel disease are linked to CDTHL.

 

DRUGS

Early entry of anagen hair follicles into telogen (immediate anagen release) represent a main mechanism of drug induced TE. In many cases, shedding starts 3 months after initiation of the drug and recovery from TE can be expected around 3 months after the termination of the causative drug.

The most prominent offenders are retinoids (acitretin and isotretinoin), anticonvulsants (e.g. phenytoin, valproic acid, carbamazepine) antithyroid medications (propylthiouracil, methimazole), anticoagulants (heparin and warfarin), discontinuation of oral contraceptives, and interferons.

 

 

PATHOGENESIS

 

Headington described five functional types of TE

 

Immediate anagen release

Immediate anagen release occurs when hair follicles are stimulated to leave anagen and enter telogen prematurely resulting in increased shedding 2-3 months later. This premature termination of anagen and entry into telogen can be a common mechanism for acute TE such as physiologic stress, severe illness, or drug-induced hair loss. Recovery can be expected once external insults are withdrawn and the normal hair cycle restarts.

 

Delayed anagen release

Delayed anagen release is due to prolongation of anagen resulting in delayed but synchronous onset of heavy telogen shedding. The most common example is telogen gravidarum, where anagen prolongation occurs under the effect of pregnancy hormones. A similar state occurs after discontinuation of contraceptive pill. Postpartum, the hormonal drive is removed and many hairs shift to telogen, resulting in increased shedding 3-4 months later.

 

Immediate telogen release

Immediate telogen release generally occurs with drug induced shortening of telogen leading to follicles reentering anagen prematurely. Hence, a massive release of club hairs (exogen) occurs as seen when starting therapy with topical minoxidil.

 

Short anagen syndrome

Short anagen syndrome is characterized by an idiopathic shortening of anagen duration, leading to persistent telogen hair shedding. This mechanism is considered responsible for majority of cases with CTE with mild persistent hair loss and inability to grow the hair long. 

 

Delayed telogen release

Delayed telogen release is characterized by a prolonged telogen and delayed transition to anagen. It occurs in animals with synchronous hair cycles but may be responsible for seasonal hair loss in humans.

 

 

HAIR EXAMINATION

 

Hairs pull Test

Hair "pull test" is a simple method and should be performed as part of the physical examination in patients with suspected TE. The test is helpful to detect active hair shedding. About 50–60 hair fibers close to the skin surface are grasped and  the hairs from the proximal to distal ends are tugged. Normally, only two or three hairs are pulled out by this method. In the presence of abnormal shedding, more than 10% hair (6–10 hair) can be easily pulled out from any part of the scalp, if the patient has not shampooed for more than 24 h. The test should be performed in four regions of the scalp: the frontal, occipital, and both temporal regions. The hair should not be shampooed for at least a day. 

A negative test (six or less hairs/less than 10% obtained) indicates normal shedding, whereas a positive test (more than six hairs or 10% obtained) indicates definite active shedding of hair during the acute phase. In patients with AGA the test is usually negative. A positive pull test suggests the possibility of acute telogen effluvium. The morphology of the hair root is examined with a light microscope to determine, if the hairs break off (blunt ends) or came out as club hairs (telogen hair).

 

Trichogram

This technique is a simple method of quantifying hair loss by comparing the proportion of anagen to catagen and telogen hairs. For accurate measurement, patients should avoid washing their hair 3–4 days prior the test. Also perms, dyes, or straightening of hair can alter results and have to be avoided at least 6 weeks prior. A group of about 25–50 hairs should be grasped with a needle holder close to the scalp and plucked sharply in the direction of the hair. The proximal ends of the hair shafts are place on a glass slide in a drop of water and covered with a cover slip. Alternatively, a solution of 1% dimethyl cinnamaldehyde in 0.5 N hydrochloric acid can be used, which stains the anagen hairs red due to the presence of protein bound citrulline in the inner root sheath. The roots are than examined by light microscopy with 100-fold magnification. Ten to twenty percent of telogen hair can be regarded as normal.  Acute TE can be suggested if the telogen count exceeds 25%.

 

Trichoscopy (Dermoscopy)

This technique enables the distinction of clinically resembling disorders, including TE, androgenetic alopecia (AGA) and diffuse alopecia areata (AA). The decrease in hair density and empty hair openings (active phase) or short re-growing hairs (recovery phase) may be seen in acute TE. Presence of thick terminal hairs goes in favor of acute TE, whereas in chronic TE, terminal hairs tend to become thinner. Diagnosis of chronic TE is based on exclusion rather than specific diagnostic criteria. A critical feature is the presence of less than 20% of hair diameter diversity. Signs suggestive of AGA, such as diversity of hair shaft diameter affects > 20% of the hairs, brown halos around hair shafts (peripilar sign) and in AA yellow dots, black dots, broken hairs of similar lengths and exclamation point hairs, should be absent.

 

Histology

The histological findings in TE are a normal total number of hairs, total number of terminal (large) hairs, an increase in the telogen hair ratio, the hair shafts are of equal diameter (unlike AGA),  and absence of inflammation and scarring. The telogen hair count greater than 20% supports the diagnosis of TE. Normal telogen counts are typically in the range of 6-13%.

 

Laboratory tests

Laboratory tests should be performed when the cause is not identified or needs to be evaluated for its status. Recommended tests include urine analysis, complete blood cell count, ESR, total protein and albumin, SGOT, SGPT,  BUN/creatinine, lactate dehydrogenase, serum ferritin and zinc, T3, T4, thyroid-stimulating hormone, ANA, sex hormones (testosterone, LH and FSH in females), prolactin, C-reactive protein,  syphilis and HIV tests.

Microscopic features of telogen and anagen hair.

A Telogen shaft showing a club-shaped bulb. B Anagen shaft with attached root sheaths, demonstrating a pigmented and distorted bulb. M, matrix; I, inner root sheath; O, outer root sheath. 

 

Prognosis and clinical course

Both acute and CTHL usually resolve once trigger factors are eliminated. However, in CTE there in no trigger. Women with TE are often most concerned about complete baldness. The patient has to be reassured that the condition does not lead to complete baldness and that the hair likely grows back around 6 months after removal of the initiating trigger. The patient should understand that the condition is reversible, but that the shedding may persist for a few weeks or months once the initiation factor is eliminated.

 

Treatment

 

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·       Treatment for TE is primarily reassurance and counseling. 

·       If attempts at identifying a specific cause have been fruitful, one should correct them. 

·       An expectant management and observation are usually appropriate as shedding is expected to cease within 3-6 months and thereafter recovery should be complete.

 

Counseling of the patient 

·       Patient's frustrations should be addressed and an assurance that TE will not lead to baldness is helpful. 

·       Frustration generally arises from the inability to comprehend that a completely healthy person can still have hair loss; that hair loss could be a result of untreated medical concerns; and that mixed forms of hair loss can exist

·       One has to deal with many myths and misinformation surrounding hair loss. 

·       The patient needs a brief discussion explaining the diagnosis and treatment options. 

·       Being a cosmetic concern, the degree of disability due to hair loss varies widely. 

·       Psychosocial counseling has been claimed to be the best treatment as it is the safest and least invasive way to address the psychosocial impact. 

·       Hair regrowth being slow (1 cm per month); the patient should be counseled to have appropriate expectations

 

 Management of Telogen effluvium 

·       Telogen effluvium is a reversible disorder once the initiating factor is eliminated 

·       No specific treatment is needed. 

·       In the absence of a documented etiopathogenesis, no treatment can be endorsed, but a course of topical corticosteroids could be tried.

 

ATE management 

·       ATE usually remits within few months in 95% of cases. A small proportion of TG cases may experience persistent, episodic shedding as some follicles may not revert to an asynchronous growth pattern. 

·       A full recovery may also be compromised in senile women due to the concurrence of AGA and aging of follicles.

·       In addition, ATE not remitting for prolonged periods may actually be early AGA or diffuse alopecia areata. 

·       Moreover, on many occasions, an episode of ATE may unmask an underlying AGA.

 

Potential treatment options 

·       Based on the pathogenesis of TE, potential therapeutic options include inhibition of catagen (so as to prolong anagen); induction of anagen in telogen follicles; or inhibition of exogen (to reduce hair shaft shedding). 

·       Neither of the currently available Food and Drug Administration (FDA) approved standard hair drugs (finastetride and minoxidil) are highly efficient catagen inhibitors or anagen inducers. 

·       However, what can assuredly be done is the exclusion of catagen inducing drugs (beta-blockers, retinoids, anticoagulants, or antithyroid drugs) or catagen-inducing endocrine disorders (thyroid dysfunction, hyperandrogenism, or hyperprolactinemia). 

·       Substitution therapy for catagen promoting deficiencies like those of iron, zinc, estradiol, or proteins can also be initiated. 

 

Vitamin supplements 

·       At this time, there are no proven vitamins or supplements for any form of hair loss. 

·       If there is a measurable deficiency such as IDA, then its replacement may help. 

·       However, a balanced diet and stable body weight are most important measures. 

·       Biotin supplementation has been shown not to affect TE.

 

 Iron replacement 

·       Controlled studies regarding efficacy of replacement of iron or thyroxine on the outcome of TE, are also lacking, although some benefit has been claimed. 

·       It has been suggested that maintaining serum ferritin above 40 ng/dL (70ng/dl by some authors) helps reverse hair loss. An adequate dietary intake and, if required, oral ferrous sulfate, 300 mg (60 mg elemental iron) taken 3-4 times daily is a widely accepted and cost effective initial therapy. 

·       It should lead to rise in hemoglobin concentration by 2 g/dL in 3-4 weeks.

·       In cases with poor response, causes like poor compliance, misdiagnosis, malabsorption, coexisting anemia, and continued blood loss should be assessed. Iron supplementation needs to be continued for 3-6 months until iron stores are replenished. Unnecessary long-term iron supplementation can lead to iron overload.

 

Role of antioxidants 

·       The proposed role of antioxidants or other supplements has not been proven by any creditable evidence. Green tea (containing polyphenolic compounds) has been reported to improve patchy hair loss in mice. 

·       However, no controlled studies are available in humans. 

 

TE and FPHL 

·       TE often uncovers female pattern hair loss (FPHL), bringing the patient in for shedding and thinning on the crown. 

·       This is the most common combination of hair loss and should be addressed with reassurance if the telogen is still occurring, followed by examination 6 months later for improvement.

·       Treatment of FPHL can be started if hair loss has not started to improve by the 6-month follow-up. Topical 2% or 5% minoxidil solution 1 mL twice daily can be helpful, especially in women with CTE; however, increased in telogen hair may be experienced 2-6 weeks after treatment initiation.

 

Stress reduction for stress induced TE 

·       No specific therapeutic intervention, which could prevent stress-induced premature onset of catagen, is currently available for stress-induced TE. 

·       Topical minoxidil could be a reasonable candidate drug in this category as it is known to prolong anagen. 

·       In addition, in vivo studies in mice have demonstrated that minoxidil can down regulate stress-induced hair growth inhibitory and catagen promoting changes along the "brain-hair axis." 

·       Its clinical efficacy in humans with respect to TE remains to be investigated. In addition, stress-coping strategies may help, however, controlled data in this respect is lacking.

·       Complex, comprehensive, and careful management beyond drug prescription in order to alleviate clinical symptoms and the concomitant psychological implications may go a long way in helping the patients.

 

A novel cosmetic treatment 

·       A novel cosmetic treatment for thinning hair in TE has been reported by Davis et al. 

·       It comprises of a leave-on technology combination (caffeine, niacinamide, panthenol, dimethicone, and an acrylate polymer [CNPDA]), which significantly increases the diameter of individual, existing terminal scalp hair fibers by 2-5 μm, yielding an increase in the cross-sectional area of approximately 10%. 

·       Beyond the diameter increase, the CNPDA-thickened fibers demonstrated the altered mechanical properties characteristic of thicker fibers and better ability to withstand force without breaking. 

·       However, its efficacy in TE remains to be established.

 

CDTHL treatment 

·       CDTHL seen in thyroid disorders is generally reversible when euthyroid state is restored, except in long-standing hypothyroidism where hair follicles may have atrophied. 

·       Thyroid peroxidase antibodies have been demonstrated in a significant percentage of TE patients. 

·       Additional tests of iron status including erythrocyte zinc protoporphyrin concentration, transferrin concentration, serum iron concentration, and transferrin saturation may be required. 

·       The cause of iron deficiency must also be identified to ensure effective management.

 

End note 

·       Improved understanding of causes and management of TE has led to improved outcomes 

·       The outcomes have improved as knowledge has improved about the factors that control hair follicle cycling. 

·       The role of novel therapies reported, remain to be studied in further detail.