eMedicine Specialties > Dermatology > Diseases of the Adnexa

Anagen Effluvium

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Bryan D Seiff, MD, Staff Physician, Department of Ophthalmology, NY Presbyterian Hospital-Cornell; Pere Gascon, MD, PhD, Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain

Updated: Sep 2, 2009

Introduction

Background

Normal human hairs can be classified according to the 3 phases of their growth cycle: anagen, catagen, and telogen. Anagen hairs are in a growing phase, during which the matrix cells of the hair follicle undergo vigorous mitotic activity. These hairs have long, indented roots covered with intact inner and outer root sheaths, and they are fully pigmented.

Toward the end of the anagen phase, the amount of pigment decreases at the base of the follicle, which expands to form a keratinized club. Then, the hair enters the catagen phase, a transitional phase in which mitotic activity decreases. The follicle separates from the dermal papilla and the capillary plexus and moves upward within its connective tissue sheath toward the epidermis. The resulting telogen hairs, or club hairs, are in a resting phase. These hairs have short, club-shaped roots that anchor them in the follicle. They lack root sheaths and show depigmentation of the proximal part of the shaft.

The hairs continue in this resting state until the follicle spontaneously reenters the anagen phase. At this point, the club hairs are forced out by growing hairs underneath them, and the cycle begins anew. The cycle is not synchronous throughout the scalp; patches of hair may be synchronized. The length of each phase of the cycle, as well as the length of the entire cycle, varies with the site and the age of the patient. In the scalp, for example, the average length of the anagen phase is 1000 days; that of the catagen phase, only a few days; and that of the telogen phase, 100 days. Of the 100,000 hairs on the average scalp, 10-15% are in the catagen or telogen phase at any time. Most hair follicles are in the anagen stage at any given time.

Pathophysiology

Hair loss can be classified according to the stage of the hairs shed. Telogen effluvium is defined as the early and excessive loss of normal club hairs from normal resting follicles in the scalp. This hair loss usually results from trauma to the normal hair as a result of a stressor such as parturition, surgery, or fever that causes an abnormally large percentage of hairs to move into the catagen and telogen phases. When anagen restarts 2-4 months later, the club hairs are pushed out and lost, causing a temporary diffuse thinning of the scalp hair.

Anagen effluvium occurs after any insult to the hair follicle that impairs its mitotic or metabolic activity. The hair loss is usually the result of an exposure to chemotherapeutic agents such as antimetabolites, alkylating agents, and mitotic inhibitors that are used to treat cancer, although it is not the only type of chemotherapy induced – hair loss in these patients.^{[1 ]}
 
The inhibition or arrest of cell division in the hair matrix can lead to a narrow, weakened segment of the hair shaft that is susceptible to fracture with minimal trauma. It can also result in complete failure of hair formation. The hair bulb itself may be damaged, and the hairs may separate at the bulb and fall out. Only actively growing anagen follicles are subject to these processes. This form of alopecia is more common and severe with combination chemotherapy than with the use of a single drug, and the severity is generally dose dependent. Anagen effluvium also occurs in persons with alopecia areata as the result of the inflammatory insult to the matrix.

The characteristic finding in anagen effluvium is the tapered fracture of the hair shafts. The hair shaft narrows as a result of damage to the matrix. Eventually, the shaft fractures at the site of narrowing.

Anagen effluvium is an uncommon symptom of pemphigus vulgaris.^{[2 ]}The hair follicle is a preferential target for pemphigus autoantibodies because the desmosomal proteins are overexpressed in the follicular epithelium. The ensuing intercellular cleavage causes the anagen hairs in lesional and perilesional areas to fall out.

Clinical

History

• Patients present with diffuse hair loss after an exposure to drugs or toxic chemicals. Chemotherapeutic agents are most commonly responsible for hair loss. The most severe hair loss occurs in association with doxorubicin, the nitrosoureas, and cyclophosphamide. Hair loss usually begins 7-14 days after a single pulse of chemotherapy. The hair loss is clinically most apparent after 1-2 months.
• The patient's full dermatologic, systemic, and family histories should be obtained to rule out other causes of hair loss, including malnutrition, iron deficiency, endocrine and metabolic disorders, collagen disease, infections (eg, syphilis), and widespread skin disease.
• Anagen effluvium may be an uncommon symptom in a patient with pemphigus vulgaris.
• A variety of medications may cause hair loss, stimulate hair growth, or induce changes in hair shape and color. Drug-induced hair loss is usually a consequence of a toxic effect of the drug on the hair matrix. Although many drugs have been occasionally described to produce hair loss, the relationship between drug intake and hair loss has only been proven for a few agents. The type of hair loss (ie, telogen effluvium, anagen effluvium, or both) depends on the medication, its dosage, and patient susceptibility.

Physical

• Anagen effluvium is a nonscarring alopecia that leaves the follicular ostia intact.
• Most hair follicles are in the anagen stage at any given time; therefore, anagen alopecia affects a large percentage of the scalp.
• Some chemotherapeutic agents can also induce telogen effluvium.
• The combination of telogen effluvium and anagen effluvium can result in complete baldness.
• The diffuse alopecia of anagen effluvium can be distinguished from androgenetic alopecia, which is characterized by frontotemporal thinning followed by hair loss in the crown.
• The hair and scalp should be thoroughly inspected to rule out local disease.
  • Any erythema, scale, pustules, bogginess, sinus tract formation, or obliteration of the follicular openings should be noted.
  • Any of these findings may indicate another cause of the alopecia.

Causes

Chemotherapeutics used to treat cancer are the most common causes of anagen effluvium.^{[3,4,5 ]}

• The most severe alopecia is caused by doxorubicin, the nitrosoureas, and cyclophosphamide. Other causative agents include bleomycin, dactinomycin, daunorubicin, fluorouracil, and methotrexate.
• Other medications that can cause anagen effluvium include bismuth, levodopa, colchicine, and cyclosporine.
• Exposure to chemicals such as thallium, boron, and arsenic can precipitate anagen effluvium.
• Causes of anagen arrest also include radiation therapy, endocrine diseases, alopecia areata, cicatrizing disease, and trauma or pressure.
• Pemphigus vulgaris is reported to be a cause of anagen effluvium.

Differential Diagnoses

Other Problems to Be Considered

Hypothyroidism
Hyperthyroidism
Hypopituitarism
Diabetes mellitus
Sézary syndrome
Lymphoma
Protein malnutrition
Iron deficiency
Collagen disease
Endocrine and metabolic disorders
Infections (eg, syphilis)
Widespread skin disease

Because most scalp hair is in anagen at a given time, and telogen effluvium is dependent on the transition from anagen to telogen, with subsequent release of telogen hairs, it has a latent period of months, and the hair loss is usually subclinical, involving less than 50% of hairs.^{[1 ]}

Workup

Laboratory Studies

• A few select laboratory studies may be performed, as indicated by features of the history or physical findings.
• Serologic tests may include the following:
  • Iron studies
  • Thyroid function tests^{[6 ]}
  • Rapid plasma reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests
  • Antinuclear antibody (ANA) tests
• Serum and urine amino acid levels may be determined.
• If tinea capitis is a concern in the differential diagnosis, microscopic examination for fungal elements and culture for fungi may be performed.^{[7 ]}

Procedures

• Anagen effluvium can be distinguished from telogen effluvium by means of the pull test
  • To perform this test, firmly grasping 40 hairs between the thumb and forefinger and slowly pull on them to remove them, causing only mild discomfort to the patient.
  • Then, a trichogram is used to quantify the ratio of terminal anagen hairs to telogen hairs.
  • Anagen and telogen hairs can often be identified with the naked eye, but any doubts can be resolved by means of light microscopy.
  • Anagen hairs have long indented roots covered with intact inner and outer root sheaths, and they are fully pigmented.
  • Telogen hairs have short, club-shaped roots. They lack root sheaths and show depigmentation of the proximal part of the shaft.
  • Fewer than 4-6 telogen hairs are typically present. A greater number of telogen hairs indicates a shift toward the telogen phase and suggests a probable diagnosis of telogen effluvium.
• An alternative to is perform a gentle pull test or examine hairs removed by combing. The presence of tapered fractures is diagnostic of anagen effluvium.
• Anagen effluvium can be distinguished from other forms of alopecia on the basis of the histologic changes on horizontal sections.
  • A 4-mm punch biopsy sample of the scalp contains 25-50 follicles for inspection.
  • Less than 15% of the follicles are normally in the telogen phase. A normal anagen-to-telogen ratio in a patient with hair loss is characteristic of anagen effluvium.
  • A finding of greater than 15% of follicles in the telogen phase indicates a significant shift toward telogen in most individuals. This finding suggests telogen effluvium.
  • The follicles should show no signs of inflammation, dystrophic changes of the inner sheath, or traction. These features permit the distinction of anagen effluvium from alopecia areata, androgenetic alopecia, and traction alopecia.

Histologic Findings

Anagen hairs have long, indented roots covered with intact inner and outer root sheaths. These hairs are fully pigmented. Telogen hairs have short, club-shaped roots. These hairs lack root sheaths and show depigmentation of the proximal parts of the shaft.

Treatment

Medical Care

• Although topical minoxidil is not effective in preventing chemotherapy-induced alopecia, it shortens the period of baldness by about 50 days.^{[8 ]}
• Scalp cooling may be used, accomplished either with cooling agents applied via a cooling cap that is changed several times or by continuous cooling of the scalp with cold air or liquid.^{[1 ]}
• The application of a pressure cuff around the scalp and local hypothermia retard anagen arrest, if these measures are implemented during the infusion of medication.
  • These measures do not prevent anagen arrest.
  • The pressure cuff and local hypothermia presumably decrease blood flow in the scalp and hinder the delivery of medication to this site.
  • However, because the scalp may act as a sanctuary for circulating malignant cells, patients with leukemia, lymphoma, and other hematologic malignancies are generally not suitable candidates for these procedures.
• A medical corrective preparation makeup can be applied to camouflage eyebrow alopecia induced by chemotherapy and to improve self-esteem.^{[9 ]}
• University of Texas has published guidelines on treating adult hair loss disorders: Recommendations to diagnose and treat adult hair loss disorders or alopecia in primary care settings (non pregnant female and male adults).^{[10 ]}

Medication

The goal of pharmacotherapy is to shorten the period of alopecia resulting from chemotherapy. Sadly, no treatment appears to be generally effective in preventing this secondary effect of chemotherapy. In rodent models, localized administration of heat or subcutaneous/intradermal injection of geldanamycin or 17-(allylamino)-17-demethoxygeldanamycin induced a stress-protein response in hair follicles and effectively prevented alopecia from doxorubicin (Adriamycin), cyclophosphamide, paclitaxel (Taxol), and etoposide.^{[11 ]}Hopefully, localized hair-saving treatment can be developed for humans that does not negatively affect chemotherapy efficacy.

Peripheral vasodilators

Minoxidil directly dilates the peripheral vessels. Although the exact mechanism of action for promoting hair growth remains unknown, increased blood flow to the hair follicles may affect their metabolism and growth cycle and thereby prevent hair loss.

Minoxidil (Rogaine)

Relaxes arteriolar smooth muscle, causing vasodilation; hair growth possibly secondary to vasodilation. Available in 2% and 5% solutions; 5% solution recommended only for men.

Dosing

Adult

Apply 1 mL to scalp bid

Pediatric

Not established

Interactions

Concurrent guanethidine, diuretics, or hypotensive agents may result in additive hypotension

Contraindications

Documented hypersensitivity; pheochromocytoma; acute MI; dissecting aortic aneurysm

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May exacerbate angina pectoris; caution in pulmonary hypertension, congestive heart failure, coronary artery disease, significant renal failure, impaired liver function, and patients >50 y; common adverse effects include contact dermatitis, itching, and skin irritation

Follow-up

Inpatient & Outpatient Medications

• Although topical minoxidil is not effective in preventing chemotherapy-induced alopecia, it shortens the period of baldness by about 50.2 days.

Deterrence/Prevention

• The application of a pressure cuff around the scalp and local hypothermia retard anagen arrest, if these measures are implemented during the infusion of the causative medication (see Medical Care).
• The discontinuation or avoidance of the causative drug reverses anagen effluvium.
• Bleiker et al did not achieve success in a trial of the possible prophylactic effects of pretreatment with calcipotriol before chemotherapy.^{[12 ]}

Prognosis

• Anagen effluvium is entirely reversible, with hair regrowth typically occurring after a delay of 3-6 months.^{[1 ]}
• Upon the cessation of drug therapy, the follicle resumes its normal activity within a few weeks.
• Mitotic inhibition apparently stops the reproduction of matrix cells, but it does not permanently destroy the hair.
• In some cases, hair regrows despite continued or maintenance therapy.
• On occasion, the color and texture of the hair that regrows after chemotherapy-induced alopecia is different from those of the original hair.

Patient Education

• Drug-induced alopecia can be psychologically devastating to a patient. Patients have even refused possibly palliative or life-saving treatments because they could not accept the temporary or prolonged baldness.
• Patients must be warned of the potential for hair loss when they undergo treatment with any of the medications responsible for anagen effluvium (see Causes).
• Patients should also be reassured that the hair loss is temporary. Normal hair growth resumes a few weeks after the termination of treatment, although the color or texture of the regrowing hair may differ from those of the original hair.

References

1. Trueb RM. Chemotherapy-induced alopecia. Semin Cutan Med Surg. Mar 2009;28(1):11-4. [Medline].

2. Delmonte S, Semino MT, Parodi A, Rebora A. Normal anagen effluvium: a sign of pemphigus vulgaris. Br J Dermatol. Jun 2000;142(6):1244-5. [Medline].

3. Bronner AK, Hood AF. Cutaneous complications of chemotherapeutic agents. J Am Acad Dermatol. Nov 1983;9(5):645-63. [Medline].

4. Tosi A, Misciali C, Piraccini BM, Peluso AM, Bardazzi F. Drug-induced hair loss and hair growth. Incidence, management and avoidance. Drug Saf. Apr 1994;10(4):310-7. [Medline].

5. Tosti A, Pazzaglia M. Drug reactions affecting hair: diagnosis. Dermatol Clin. Apr 2007;25(2):223-31. [Medline].

6. van Beek N, Bodo E, Kromminga A, et al. Thyroid hormones directly alter human hair follicle functions: anagen prolongation and stimulation of both hair matrix keratinocyte proliferation and hair pigmentation. J Clin Endocrinol Metab. Nov 2008;93(11):4381-8. [Medline].

7. Trovato MJ, Schwartz RA, Janniger CK. Tinea capitis: current concepts in clinical practice. Cutis. Feb 2006;77(2):93-9. [Medline].

8. Duvic M, Lemak NA, Valero V, Hymes SR, et al. A randomized trial of minoxidil in chemotherapy-induced alopecia. J Am Acad Dermatol. Jul 1996;35(1):74-8. [Medline].

9. Merial-Kieny C, Nocera T, Mery S. [Medical corrective make-up in post- chemotherapy]. Ann Dermatol Venereol. Jan 2008;Spec No 1:25-8. [Medline].

10. [Guideline] University of Texas at Austin, School of Nursing, Family Nurse Practitioner Program. Recommendations to diagnose and treat adult hair loss disorders or alopecia in primary care settings (non pregnant female and male adults). National Guidelines Clearinghouse. May 2004.

11. Jimenez JJ, Roberts SM, Mejia J, et al. Prevention of chemotherapy-induced alopecia in rodent models. Cell Stress Chaperones. Spring 2008;13(1):31-8. [Medline].

12. Bleiker TO, Nicolaou N, Traulsen J, Hutchinson PE. 'Atrophic telogen effluvium' from cytotoxic drugs and a randomized controlled trial to investigate the possible protective effect of pretreatment with a topical vitamin D analogue in humans. Br J Dermatol. Jul 2005;153(1):103-12. [Medline].

13. Brandy DA. A technique for hair-grafting in between existing follicles in patients with early pattern baldness. Dermatol Surg. Aug 2000;26(8):801-5. [Medline].

14. Kemmett D. ABC of dermatology. Diseases of the hair and scalp. Br Med J (Clin Res Ed). Feb 20 1988;296(6621):552-5. [Medline].

15. Mohrenschlager M, Ring J, Kohn FM. [Acquired effluvium of head hair: common conditions in women]. MMW Fortschr Med. Oct 27 2005;147(43):37-40. [Medline].

16. Sommer M, Wilson C. Therapeutic approaches to the management of common baldness. Int J Clin Pract. Jul-Aug 1999;53(5):381-5. [Medline].

17. Spencer LV, Callen JP. Hair loss in systemic disease. Dermatol Clin. Jul 1987;5(3):565-70. [Medline].

18. Sperling LC, Mezebish DS. Hair diseases. Med Clin North Am. Sep 1998;82(5):1155-69. [Medline].

19. Walkden V. Hair and scalp conditions. Practitioner. Apr 1998;242(1585):278-81. [Medline].

20. Whiting DA. Structural abnormalities of the hair shaft. J Am Acad Dermatol. Jan 1987;16(1 Pt 1):1-25. [Medline].

Keywords

anagen effluvium, chemotherapy-induced alopecia, defluvium, telogen effluvium, hair loss, alopecia, catagen

Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Bryan D Seiff, MD, Staff Physician, Department of Ophthalmology, NY Presbyterian Hospital-Cornell
Bryan D Seiff, MD is a member of the following medical societies: Alpha Omega Alpha
Disclosure: Nothing to disclose.

Pere Gascon, MD, PhD, Professor and Director, Division of Medical Oncology, Institute of Hematology and Medical Oncology, IDIBAPS, University of Barcelona Faculty of Medicine, Spain
Pere Gascon, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, New York Academy of Medicine, New York Academy of Sciences, and Sigma Xi
Disclosure: Nothing to disclose.

Medical Editor

Günter Burg, MD, Professor and Chairman Emeritus, Department of Dermatology, University of Zürich School of Medicine; Delegate of The Foundation for Modern Teaching and Learning in Medicine Faculty of Medicine, University of Zürich, Switzerland
Günter Burg, MD is a member of the following medical societies: American Academy of Dermatology, American Dermatological Association, International Society for Dermatologic Surgery, North American Clinical Dermatologic Society, and Pacific Dermatologic Association
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic, Northside Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Rosalie Elenitsas, MD, Herman Beerman Associate Professor of Dermatology, University of Pennsylvania School of Medicine; Director, Penn Cutaneous Pathology Services, Department of Dermatology, University of Pennsylvania Health System
Rosalie Elenitsas, MD is a member of the following medical societies: American Academy of Dermatology and American Society of Dermatopathology
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

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