10/27/2013
Disclosures ALOPECIA 101 • Grants • Allergan (Investigator Initiated)
• Medicis (Investigator Initiated)
• Consulting/Advisory Board Maria Hordinsky, MD • Allergan Professor and Chair • Proctor & Gamble Department of Dermatology • Member, Pantene Institute University of Minnesota
Evidence Based Medicine Focus of Today’s Discussion
•Evaluation of the Patient with the Chief
• Lange series, Clinical Dermatology Complaint of Hair Loss • • UpToDate Cicatricial (Scarring) Alopecia • Hair Diseases • Pattern Hair Loss in Men and Women • Telogen Effluvium •Alopecia Areata
• Hair Care Habits
Important Cells for the Creation of The Regenerative Ability of Hair New Hair Follicles “The hair follicle demonstrates the unusual ability to completely regenerate itself.” Epithelial Stem Cells
•Hair grows, falls out and Dermal then regrows Cells •A plucked hair regrows Inducer Responder
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Clinical Examination
Start with a history….. •Examine the affected area •patients tend to hide their hair ….and remember, hair loss may loss or remove excess hair! occur for many reasons; your patient may have more than one contributing factor
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Questions to Ask
Ask about • Is it loss or thinning • Hair care habits • Symptoms – pain, itch, burning, is there a product relationship • Body hair – is there too much or too little? • Nail abnormalities • Menstrual cycle/Pregnancies • Medications • Diet/Supplements • Family History • Questions about androgen excess, autoimmune/endocrine diseases
Laboratory Tests
• Thyroid stimulating hormone • Complete blood count (CBC), ferritin, and iron profiles • Document the presence or absence of the following: • If indicated by history and physical examination: • Erythema, Scale, Folliculitis, Scarring • Non cycle dependent hormones such as DHEA-S • Look for new hair growth (fibers with tapered and total/free testosterone ends) or hair breakage • ANA • Perform a pull test to assess for active shedding • Other autoantibodies • Note body hair density and distribution • Document any nail abnormalities • Other: Vitamin D, Vitamin E, Thiamine, Zinc, total protein • Use Scales such as the Ludwig, Hamilton/Norwood, or others to define the extent
of the hair problem
• Take pictures
CICATRICIAL ALOPECIAS
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Neutrophilic Cicatrical Alopecias Lymphocytic Cicatricial Alopecias
• Dissecting cellulitis, • Lichen planopilaris also known as • Central centrifugal dissecting folliculitis scarring alopecia
• Frontal fibrosing • Folliculitis decalvans alopecia • Discoid lupus erythematosus
Discoid Lupus Erythematosus
Chronic cutaneous lupus erythematosus
LYMPHOCYTIC CICATRICIAL ALOPECIA TREATMENTS:
Systemic • Tier 1 Treatments: Lupus Erythematosus • Topical high potency corticosteroids/Intralesional steroids • Topical non-steroid anti-inflammatory creams(tacrolimus, pimecrolimus)
• Tier 2 Treatments • Hydroxychloroquine • Low dose antibiotics for anti-inflammatory effect • Acetretin
• Tier 3 Treatments • Cyclosporin • Mycophenolate mofetil • Prednisone
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Frontal Fibrosing Alopecia An Emerging Hair Disease
Characterized by: • regression of the hairline • perifollicular inflammation at the active margin
Frontal Fibrosing Alopecia
• First described in six postmenopausal women by Kossard in 1994
• The incidence of FFA is unknown, but experts agree that the number of women seeking diagnosis and help for this condition has markedly increased in recent years
• The etiology is unknown • most commonly detected in postmenopausal women, and thus a hormonal etiology has been suggested • This is further supported by occasional improvement with anti- androgen therapy such as the 5-alpha reductase inhibitors (finasteride and dutasteride), although patients do not typically have elevated androgen levels or other hormonal abnormalities
Staphlococcal Infections Relatively New Approach Role in the Cicatricial Alopecias?
• Pioglitzone • Widely used for type 2 diabetes mellitus (Actos)
• Can be used in non-diabetic patients
• Side effects: fluid retention, weight gain, peripheral edema • Successful use reported in case reports in the literature
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C. A. R. F. •Pattern Hair Loss in Women CICATRICIAL ALOPECIA RESEARCH FOUNDATION Is it Female Pattern Alopecia or Female 6th International Patient-Doctor Conference Androgenetic Alopecia or even another
Chicago, Illinois problem presenting clinically as pattern Friday-Sunday, April 4-6, 2014 hair loss? Host: Dr. Victoria Barbosa
www.carfintl.org
Frontal Accentuation (Christmas Tree Pattern) in Female Pattern Hair Loss
Ludwig Classification Normal density Patients with progressive stages of AGA/FPHL Olsen EA. J Am Acad Dermatol. 1999;40:106-109.
CASE #1
• 38-year-old Caucasian female
• Chief complaint: • hair loss and an itchy scalp
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CASE #2
• 24-year-old Asian female
• Chief complaint: • diffuse scalp hair loss
• Telogen Follicles
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Telogen Effluvium Functional Types Treatment of Telogen Effluvium
• Depends on controlling transitions between stages of the hair cycle. 1. Immediate anagen release • Currently topical Minoxidil (2% and 5%) are available; use 2. Delayed anagen release of this drug induces anagen differentiation. 3. Short anagen 4. Immediate telogen release • Whether the laser comb will be effective in this condition remains to be determined. 5. Delayed telogen release
• Prevention of catagen is a goal. Headington JT. Telogen Effluvium. Arch Dermatol 1993; 129: 356-363.
Chronic Telogen Effluvium HAIR LOSS AND LOW IRON STORES
• Commonly seen in middle-aged women in their fourth to Is there a relationship? sixth decades
• Associated with significant temporal thinning
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IRON SUPPLEMENTATION AND HAIR GROWTH TOTAL BODY IRON
• Distributed in 3 compartments Mouse Model with a mutation in TMPRSS6 • Functional Iron • Measured by hemoglobin concentration and hematocrit • Transport Iron • Measured by • Erythrocyte zinc protoporphyrin concentration • Transferrin concentration • Transferrin saturation (ratio of serum iron to TIBC) • Total iron binding capacity • Serum Iron • Storage • Represents the body’s iron reserves that are bound to ferritin and hemosiderin and best measured by a serum ferritin concentration
The serine protease TMPRSS6 is required to sense iron deficiency CURRENT CLINICAL PRACTICE
• Decision to treat is based on clinical judgment
• Once the decision is made, ferrous sulfate, ferrous fumerate and ferrous gluconate are all viewed as being equally effective
WHAT IF THE LEVEL DOESN’T GO UP? CASE #3 • 34-year-old African American female • If a patient with iron deficiency anemia takes ferrous sulfate 300 mg (60 mg elemental iron) 3 to 4 times a day, the hemoglobin concentration should rise approximately 2 g/dL • Chief complaint: after 3-4 weeks; replenishing iron stores may take 3 to 6 months. • ongoing scalp hair thinning and itching
• If there isn’t a response, consider • Poor compliance • Misdiagnosis • Malabsorption • Continued blood loss • Coexistence of another cause for the anemia • Scalp biopsy for vertical and horizontal sectioning
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Seborrheic Dermatitis ANDROGENETIC ALOPECIA
“Pattern Alopecia”
Frontal Accentuation Male (Christmas Tree Pattern) Androgenetic in Female Pattern Hair Loss Alopecia
Hamilton Norwood Classification
Normal density Patients with progressive stages of AGA/FPHL Olsen EA. J Am Acad Dermatol. 1999;40:106-109.
Treatment of Androgenetic Alopecia • SURGICAL • COSMETIC • DEVICE • Laser Comb (FDA approved) • MEDICAL • Minoxidil (Rogaine) • 2% • 5% (Extra Strength) • 5-alpha reductase inhibitors • Finasteride, 1 mg (Propecia, Merck) – a type 2 5-alpha reductase inhibitor – Not effective at this dose in post-menopausal women
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Low-Level Light Therapy (LLLT)
• Mitochondrial photochemical reactions • Restores ATP levels, generates signaling
• Rescues cells from hypoxia, ischemia, oxidative stress, Alopecia Areata apoptosis
• Stimulates stem cells to divide and migrate • FDA approved for androgenetic alopecia
In alopecia areata IMMUNOLOGY Anagen when immune Hair privilege is lost, A hallmark of Follicle alopecia the anagen hair areata: follicle is seen as the Invader! •peribulbar lymphocytes around anagen follicles White Blood Cell
ALOPECIA AREATA:
ALOPECIA AREATA • There is no “best” treatment
• There is no FDA approved therapy for this disease Patchy or Ophiasis Alopecia Areata • Recent studies examining the efficacy of biologics in this disease have not been
rewarding • So what do you do?
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PATCHY ALOPECIA AREATA: EXTENSIVE ALOPECIA AREATA:Treatments TREATMENT • Prednisone/Pulse Methylprednisolone • Topical or Intralesional Corticosteroids • Topical Minoxidil • Minoxidil Solution- 2% or 5% • PUVA/Narrow Band UVB • Anthralin • Other Phototherapies • Combination Therapy – Excimer laser/Fractional Photothermolysis Laser – PDT • Steroids in Shampoo Formulations – Infrared irradiation • Immunotherapy • Methotrexate • Cyclosporine • Sulfasalazine • Combination Therapy • Prostaglandin Analogues • Biologics • Treatment based on histopathology
SCALP BIOPSY
• No?
• Yes?
Histopathology: Normal Human Scalp: Horizontal Section
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Intralesional Kenalog
• Local injection of corticosteroids such as triamcinolone acetonide (Kenalog) into lesions of patchy AA has been a preferred treatment since the late 1950s and is considered standard of care.
• Side effects tend to be local with a potential for adrenal suppression.
NEW TREATMENT APPROACHES
Based on Pathophysiology and Genome Wide Scanning Studies (GWAS)
Alopecia Areata Registry FIRST AND SECOND TIER REGISTRATION • Led To New Directions Based on Genome • FIRST TIER – Information on the following is collected: • gender, ethnicity, family participation, disease, and group Wide Association Study (GWAS) Data and categories. Information from the Alopecia Areata • SECOND TIER - Patients who met the inclusion Registry – to be discussed criteria for Second Tier Registration were chosen from this database for: • a clinical visit, acquisition of additional medical history, physical examination and blood draws including establishment • Evolved to the National Alopecia Areata of lymphoblastoid cell lines. Registry, Biobank, & Clinical Trials Network (Registry)
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Overview of Total Registration Alopecia Areata Research Progress
• First Tier Registrants:
• 9,237 with alopecia areata • Dr. Angela Christiano and team identified eight • 1,779 unaffected controls genes that contribute to alopecia areata • Second Tier Registrants: • 3,513 completed Second Tier Registration • Registry provided the 1,054 cases collected for this • 396 unaffected unrelated controls research • 461 unaffected relatives Other • Genes also associated with rheumatoid arthritis, • 53 participants ascertained for the scalp biopsy type 1 diabetes, and celiac disease study • Autoimmune diseases with pre-existing treatments • 41 multiplex families (258 probands and family members) ascertained
May, 2013
GWAS and follow-up studies show evidence for associations of alopecia areata with genomic regions that play a role in the immune system and/or hair follicle ULBP3 Gene Region or Cluster Full name: Implicated Genes Immune System Cytomegalovirus UL16-binding protein (ULBP3) gene cluster • CTLA4 & ICOS1 on chromosome 6q25.1. • IL-2/IL-211,2 • Implicated genomic regions • HLA1,3 contain genes with T-cell • ULBP3 & 61,2 1 related functions in the immune • IL-2RA (CD25) system • Eos (IKZF4) & ERBB31,2 New finding • SPATA53 2 Strong effect Hair Follicle • IL-13 • CLEC16A (KIAA0350)2 • Implicated genomic regions • STX171,2 contain genes for natural killer • PRDX51,2 The ULBP genes make the NKG2D-activating ligand or activating ligands including signal. 1Petukhova et al. 2010 ULBP3 and ULBP6, as well as 2Jagielska et al. 2012 (Petukhova et al., 2010) STX17 and PRDX5 3Forstbauer et al. 2012
Danger Signals: ULBP3 Expression in the Hair ULBP in AA Patients Follicle
• Looked at scalp of patients with AA. • Studied whether genes were turned on or expressed in the scalp.
• Found higher levels of ULBP3 expressed in the hair follicles during active AA.
(Petukhova et al., 2010)
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Emerging Directions Bimatoprost and Latanoprost
• Targeting Interleukin 15 • Both have shown some promise in treating eyelash alopecia areata • Targeting intracellular protein kinases, such as the JAK family of tyrosine kinases • More studies are needed • Includes ruxolitinab (Jakinib) and Tofacitinib
• Blocking co-stimulatory signals • Abetacept also known as Orencia
Light Therapy: Excimer Laser OFFER PATIENTS:
• Efficacy has been demonstrated in some patients Clinical Trials
Information about the National Alopecia Areata • Moving to multi-center clinical trials Foundation (NAAF) supported by the National Alopecia Areata Foundation
HAIR ABNORMALITIES RELATED TO HAIR CARE HABITS •Too much trauma from heat, use of relaxers, environmental damage, excessive brushing, overuse of hair care products, etc. CAN RESULT IN STRUCTURAL HAIR ABNORMALITIES AND HAIR FIBER BREAKAGE
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Trichoptilosis-post-traumatic Bubble hair
Extensive loss of cuticle leads to fraying and splitting of hair shaft
Overheating damp hair causes moisture in hair to boil !
Dermatomyositis and the Scalp Case Presentation o 40 year old Caucasian female with a diagnosis of Patient Presentation dermatomyositis of 5 years presents with severe scalp
pruritus of 4 years:
• Scalp exam: diffuse erythema and fine scale Dermatomyositis(DM) manifests with scalp • Skin exam: Gottron's papules and a diffuse involvement and pruritus that can be difficult to poikiloderma of her neck, face, and upper back manage and produces intense patient suffering • Neurologic exam: no prominent muscle and discomfort weakness found
o Past medical history was negative for diabetes, alcoholism and neurologic diseases other than dermatomyositis
o Normal Laboratory serum tests: complete blood count, basic metabolic panel, thyroid function testing
Case Presentation Cont. Normal Scalp Biopsy
o Multiple failed treatments for her scalp itch include: • Topical and systemic steroids • Mycophenolatemofetil • Dapsone • Methotrexate • Intravenous immunoglobulin • Hydroxychloroquine
o Current treatment : Hydroxychloroquine 200 mg twice per day, Methotrexate 25mg weekly, Ketoconazole 2% shampoo every other day, and Folic acid supplementation
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