internal medicine

Rev. Med. Chir. Soc. Med. Nat., Iaşi – 2014 – vol. 118, no. 1
INTERNAL MEDICINE - PEDIATRICS
UPDATES
ALOPECIA – A CHALLENGE FOR DERMATOLOGISTS
Daciana Elena Brănișteanu1,3, Cătălina Maria Voicu 3, D.C. Brănișteanu2
University of Medicine and Pharmacy “Grigore T. Popa” - Iasi
Faculty of Medicine
1. Discipline of Dermatology
2. Discipline of Ophthalmology
“Sf. Spiridon” Emergency Hospital Iaşi
3. Department of Dermatology
ALOPECIA - A CHALLENGE FOR DERMATOLOGISTS (Abstract): Alopecia is a loss of
hair in the areas where it normally grows. It has to be distinguished from atrichia, the co ngenital absence of hair due to the absence of hair follicles, and hipotrichosis, scarcity or a bsence of hair in some congenital diseases. Alopecia is either scarring, when the skin appears
atrophic, scaling, and smooth and the hair follicles are absent, or nonscarring, whe n hair loss
is not accompanied by the destruction of hair follicles. This paper is a review of all types of
alopecia and their features in an attempt to make them easier to identify and differentiate.
Keywords: ALOPECIA, ANDROGENIC ALOPECIA, ALOPECIA AREATA.
Hair is an esthetic element with important psychosocial impact in both women
and men, regardless of age. All hair disorders are actually hair follicle disorders.
Alopecia is a loss of hair in the areas it
normally grows. It has to be distinguished
from atrichia, the congenital absence of
hair due to the absence of hair follicles, and
hipotrichosis, scarcity or absence of hair in
some congenital diseases.
Alopecia is either scarring (tab. I), when
the skin appears atrophic, scaling, smooth,
and the hair follicles are absent, or nonscarring, when hair loss is not accompanied by
the destruction of hair follicles; nonscarring alopecia may be localized or diffuse
(1, 2, 3) (tab.II).
Sometimes, alopecia and hypotrichosis
together with other skin and adnexal
changes are part of a congenital syndrome.
The growth cycle of the hair follicle differs depending on body area; thus, scalp
hair has 3 phases of unequal duration:
anagen (3-5 years), catagen (2-3 weeks)
and telogen (3-4 months). Approximately
85% of hair follicles are in the growth
phase (anagen) and 70-100 hairs are shed
daily (telogen). Hair follicles of the eyebrows, trunk and limbs have a similar duration of anagen and telogen phases (6
months). The growth cycle of the hair follicle is influenced by a number of inhibitory
and stimulatory factors.
The onset of anagen phase recapitulates
the molecular events during hair follicle
development, and insulin like growth factor
1 (IGF-1) and fibroblast growth factor 7
(FGF-7) have important roles in their development and cycling. The length of hair
is directly proportional to the duration of
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Daciana Elena Brănișteanu et al.
anagen cycle, and the cessation of this
cycle is controlled by fibroblast growth
factor 5 (FGF- 5), expressed in the hair
follicle prior to the end of this phase, and
also by the system of the epidermal growth
factor receptors (EGF) .
The catagen phase is the phase during
which the hair follicle goes through a
highly controlled process of involution,
reflecting the stimulation of apoptosis in
the majority of follicular keratinocytes
and in some follicular melanocytes. Thus,
follicular melanogenesis ceases. Dermal
Nonscarring alopecia
- androgenic alopecia
- alopecia areata
- telogen effluvium
- drug-induced alopecia
- toxic alopecia
- postradiation therapy alopecia
- infectious disease
- collagenoses
- renal failure
- deficiency disorders
- dysthyroidism
TABLE I
Classification of alopecia
Scarring alopecia
- primary lymphocytic:
 chronic discoid lupus erithematosus
 lichen planopilaris
 classic pseudopelade of Brocq
 keratosis folicularis spinulosa decalvans
 alopecia mucinosa
- primitive neutrophilic:
 folliculitis decalvans
 dissecting cellulitis/folliculitis
- primitive mixed:
 keloid acne of the neck
 pustular erosive dermatitis
- secondary
 defective development
 primitive or secondary malignant neoplasms
 infections
 physical factors
Nonscarring alopecia
Androgenetic alopecia (AGA) is the
most common form of nonscarring alopecia,
accounting for 95 % of all cases of alopecia.
It affects 50% of men by age 50 years, 13%
of premenopausal women, and 37% of menopausal women. It is characterized by pro-
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papillae condense and move upward, coming to rest underneath the hair follicle
bulge and ceasing its cycle. There is a
programmed destruction of a few hair
follicles by the action of an inflammatory
cell infiltrate.
During the telogen phase the hair shaft
matures which is eventually shed from the
follicle. The percentage of hair follicles in
telogen phase varies substantially according to the body region. Later, the hair follicles reenter the anagen phase and the cycle
is repeated (4).
gressive, genetically determined hair loss,
and occurs in most men with hairline recession at the temples and vertex, and also in
some women (5). It begins in the frontotemporal region or on the vertex with a 10
time-decrease in hair diameter and hair diameter variations. In men, there is a family
Alopecia – a challenge for dermatologists
history of AGA in the first or second degree
relatives, while in women AGA is associated with micropolycystic ovary syndrome
(MPCOS), hormonal treatments, or ovarian
tumors. AGA is progressive and the rate of
hair loss is unpredictable.
In female, Ludwig classification is used
to differentiate the three clinical forms of
AGA (6, 7):
1. diffuse thinning in midline part;
2. progressive thinning in midline part
with preservation of frontal hairline;
3. oval patch of hair loss with anteroposteior long axis, surrounded by a round
band of normal density hair.
In women, vortex alopecia, male-pattern
baldness or diffuse alopecia are not very
common (5).
TABLE II
Classification of alopecia
Temporary/reversible alopecia
Permanent/irreversible alopecia
- diffuse acute:
 acute telogen effluvium
 drug-induced alopecia
 toxic alopecia
 postradiation therapy alopecia
 acute anemia
- diffuse chronic
 androgenetic alopecia
 nonandrogenetic alopecia
- chronic telogen effluvium
- drug-induced alopecia
- renal and hepatic insufficiency,
dysthyroidism
- circumscribed:
 alopecia areata
 traumatic: trichotillomania
 postinfectious: syphilis
 in chronic dermatites:
- chronic eczema, psoriasis
- primitive limphocytic:
 chronic discoid lupus eritematosus
 lichen planopilaris
 classsic pseudopelade of Brocq
 keratosis folicularis spinulosa
decalvans
 alopecia mucinosa
- primitive neutrophilic:
 folliculitis decalvans
 dissecting cellulitis/folliculitis
- primitive mixed:
 keloid acne of the neck
 pustular erosive dermatitis
- secondary
 defective development
 primitive or secondary malignant
neoplsams
 infections
 physical factors
In males, it is used Hamilton-Norwood
classification (8).
Laboratory investigations to be performed are: hormone testing (free testosterone, dehydroepiandrosterone sulphate,
prolactin, luteinizing hormone); ovarian
and adrenal gland ultrasound; serum iron
and ferritin; complete blood test; trichogram: hair strands uneven in diameter;
scalp biopsy; trichoscanning; phototrichogram.
In men a systemic treatment with 5alpha-reductase inhibitors such as Finasteride 1 mg/day, 3-6 months, or Dutasteride,
and in women a systemic antiandrogen
treatment with Diane 35, 6-12 months
alone or associated with Androcur, 6
months, spironolactone, flutamide may be
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Daciana Elena Brănișteanu et al.
initiated.
In both cases a series of topical solutions can also be used: Minoxidil 2% or
5%, Dercos-Aminexil, Chronostim; shampoos: Anaphase, Dercos; in severe cases
hair implant and camouflaging techniques
are recommended.
Alopecia areata (AA) is a nonscarring
inflammatory alopecia of unknown cause,
with an unpredictable course, a prevalence
of 0.1% among the population, and twice
more common in women.
Etiological hypotheses:
- psychosomatic factors: emotional stress
(9);
- infectious factors: cytomegalovirus;
- genetic factors: there is a 55% concordance rate in monozygotic twins, compared to no concordance in dizigotic twins
(10);
- endocrine factors: association of myxedema, diabetes mellitus type 1;
- chemical factors: interferon alfa, ribavirin, biological agents;
- association with atopy in 10% of cases;
- AA is considered a T-lymphocyte mediated autoimmune disease.
Hair strands, path gnomonic for AA,
have an "exclamation mark" appearance, 1
cm long, the distal end is darker and rough,
and proximal shaft is depigmented, narrow,
with small, poorly formed root. Their presence suggests active phase of the disease,
being absent on old alopecia areata patches
(11).
Clinical forms
AA is clinically characterized by the
presence of round non-inflammatory hair
loss areas that may enlarge and form bizarre patterns. Recent patches sometimes
are discretely erythematous or present de-
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pression in the skin, but usually the skin is
normal in appearance, but hypotonic
(Jacquet sign) .
Ophiasis AA is characterized by hair
loss patches that begin in the occipital region and then extend along the edge of the
hairy scalp, and partially or completely
wrap the scalp (fig. 1).
Fig. 1. Ophiasis alopecia areata
AA of the beard appears either independently or associated with that of the
scalp.
Alopecia totalis affects the entire scalp
and alopecia universalis covers the entire
body.
Laboratory investigations to be performed are: trichogram: dystrophic hairs;
hormonal and immunological tests for the
detection of a possible autoimmune thyroid
disease; tests for the detection of associated
atopy; histopathology: atrophic hair follicle
and the presence of perifollicular lymphocytic infiltrate; antibody determination:
antinuclear, antithyroid, antiparietal cell,
anti-endothelial.
Although there is no causal treatment, a
range of therapies with beneficial effects
can be used.
The goals of treatment are a cosmetically acceptable hair regrowth and a long-term
Alopecia – a challenge for dermatologists
therapeutic effect without severe side effects (12,13,14). Therefore, the following
can be used: immunosuppressive therapy:
corticosteroids (inhibit the production of
proinflammatory cytokines), cyclosporine
A (specific inhibitor of CD4+ lymphocyte
activation by its action on calcineurin),
macrolide immunosuppressants (inhibition
of calcineurin), photochemotherapy; topical
immunomodulatory therapy which induces
production of contact dermatitis (DNCB =
dinitrochlorobenzeon, SADBE = squaric
acid dibutylester, DPCP = diphenylcyclopropenone); minoxidil; dithranol(15).
Telogen effluvium (TE) is characterized
by temporary diffuse hair loss as a result of
shortened hair cycle and an increased number of hairs are in telogen phase. Thinning
of hair on the scalp is diffuse, sometimes
being predominant in the parietal area. It is
noted when 20-25% of the scalp hair has
falled out.
Of the causative factors we mention:
iron deficiency anemia, hyper- or hypothyroidism, delivery, inadequate diet, oral
contraception or its discontinuation, medications: hormones lipid-lowering agents,
chemotherapy, antihypertensive drugs,
psychotropic drugs, anticonvulsants, accidental exposure to toxic substances, chronic renal insufficiency, secondary syphilis
(11).
Headington has described 5 fuctional
types of ET:
- immediate anagen release and telogen
entry: psychological stress;
- delayed anagen release: after pregnancy (during pregnancy - anagen is prolonged);
- short anagen phase: idiopathic shortening of anagen;
- immediate telogen release: minoxidil
shortens the normal telogen to stimulate
hair follicles to cycle into anagen;
- delayed telogen release - prolonged
telogen followed by transient anagen (usually in animals, occasionally in humans).
Laboratory investigations to be performed are: trichogram, blood tests, total
body iron, liver tests, kidney tests, thyroid
tests, tricoscanninge.
As part of treatment, avoidance of stress
and systemic exposure to toxic substances
is recommended. Systemic treatment includes zinc, biotin, cysteine, essential fatty
acids supplements and correction of existing hormonal imbalances. The use of topical hair loss products is also recommended
(16).
Scarring alopecia
Primitive lymphocytic scarring alopecia
Chronic discoid lupus erythematosus is
two times more common in women over 40
years. It is characterized by erythematous,
squamous plaques with irregular extension
on the scalp and pruriginous scars. In the
colored people dyschromias and, more
rarely, calcification at plaque level may
appear. With time, these plaques may undergo malignant transformation to squamous cell carcinoma (17). As treatment,
systemic and topical corticosteroids, synthetic antimalarials, acitretin, dapsone,
cyclophosphamide,
cyclosporine,
and
methotrexate may be used.
Classic pseudopelade of Brocq has a
higher frequency in women aged 30-50
years. Darier and Civatte talk about this
condition as about a folliculitis, while
Rabut, Duperre, Leclerq support the theory
of pseudopelade state according to which
there can be many causes (lichen planus,
lupus) inducing the same effect. Initially,
there are small isolated atrophic plaques
that progressively enlarge, become irregu-
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Daciana Elena Brănișteanu et al.
lar, and have a tendency to confluence,
giving them the “footprints in the snow”
appearance. The plaques have polycyclic or
scalloped edges. Alopecia plaque is white,
smooth, clean, slightly depressed, scarring,
and hairs fall out imperceptibly, without
prior skin lesions (fig. 2). Disease progression is slow, and often remits spontaneously. The treatment is usually ineffective.
Autografting from unaffected areas and
scar reduction with tissues expansion can
be performed.
cia is characterized by the loss of follicular
orifices, occurrence of erythema and follicular hyperkeratosis located in the frontal
region, and a gradual progression.
Graham Little syndrome occurs in
women aged 30 to 70 years, and is characterized by scarring alopecia of the scalp
and nonscarring axillary and pubic alopecia. A few months later follicular keratosis
develops on the trunk and limbs. The therapeutic choice is the administration of cyclosporin (18).
Neutrophilic primitive scarring alopecia
Fig. 2. Classic Brocq pseudopelade
Lichen planus is an idiopathic inflammatory disease affecting the skin, hair and
nails. There are 3 clinical variants of lichen
that can cause alopecia: lichen planopilaris,
frontal fibrosing alopecia, Graham Little
syndrome.
Recent lichen planopilaris lesions are
purple erythematous-squamous papules
that, over time, are covered by follicular
hyperkeratotic plugs that eventuate into
scars. Subsequently, plugs shed and leave a
white, smooth, atrophic scar. In the hair
loss area the follicular orifices are absent,
and at its margin the hait pull test is positive. In the presence of inflammation, the
treatment implies the use of high-potency
topical corticosteroids.
Hydroxychloroquine, acitretin, and cyclosporin can also be administered.
Postmenopausal frontal fibrosing alope-
The etiology of folliculitis decalvans of
the scalp is unknown; it may occur around
the onset of puberty. Typically, the bacteriological examination of pustular secretions
identifies Staphylococcus aureus. Clinically, initially seen are follicular pustules that
evolve and heal with the formation of alopecia plaque surrounded by scales and new
follicular pustules. Treatment consists in
antibiotic therapy to eradicate Staphylococcal aureus.
Dissecting cellulitis of the scalp usually
occurs in black men aged 18 to 40 years.
Its cause is unknown. It is characterized by
the occurrence of perifolliculitis capitis
with the formation of superficial and deep
abscesses in the dermis that have the tendency to fistulizing and healing with extensive scarring (fig. 3). It can be associated
Fig. 3. Dissecting cellulitis of the scalp
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Alopecia – a challenge for dermatologists
with two other diseases that cause pilosebaceous system obstruction: hidradenitis
suppurativa hydradenitis and acne conglobata. In time, it can transform into squamous cell carcinoma. Treatment with systemic retinoids, general corticotherapy, and
later local cortico-therapy with antibiotics
is recommended.
Mixed primitive scarring alopecia
Erosive pustular dermatosis occurs in
the elderly and is of unknown etiology.
Grattan conducted a study on a group of 12
patients with erosive pustular dermatosis
and found the presence of some common
factors: local trauma and sun exposure. It
can be associated with androgenetic alopecia. Initially, a small area of the scalp becomes erythematous, covered by crust and
then superficial pustules occur on the area
that became erosive. Active areas coexist
with areas of scarring. The literature mentions the likelihood of malignant transformation to squamous cell carcinoma. Initial
treatment relies on high-potency topical
corticosteroids and later on moderatepotency ones, the use of sunscreen, zinc
supplements, calcipotriol.
Keloid acne the neck is characterized by
chronic perifollicular inflammation, more
intense in the isthmus and infundibulum,
with sebaceous gland loss. In advanced
stages there is total destruction of the pilosebaceous system; it heals with scarring.
Secondary scarring alopecia may occur
due to:
 as a result of the action of some
physical factors: radiodermatitides,
mechanical trauma, postsurgery,
thermal/electrical burns, traction alopecia;
 diseases characterized by marked
skin fibrosis: scleroderma, lichen
sclerosus, porphyria cutanea tarda,
chronic graft-versus-host disease;
 granulomatoses: sarcoidosis, necrobiosis lipoidica, granulomatous infections;
 infectious causes: bacterial: folliculitis, carbuncle/boil; fungal: kerion
celsi, scab, tinea capitis (very rare);
viral: herpes zoster, chickenpox,
HIV; protozoa: leishmaniasis; treponema: syphilis; mycobacteria: tuberculosis;
 benign tumors: cylindromas;
 primitive malignancies: basal cell
carcinoma, squamous cell carcinoma, cutaneous T-cell lymphoma;
 malignancies secondary to: kidney,
lung, gastrointestinal tumors, lymphomas, leukemias (4,19).
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NEWS
LOW VITAMIN C LINKED TO INTRACEREBRAL HAEMORRHAGE
A group of researchers leaded by Dr. St Vannier, from Pontchaillou University Hospital,
Rennes, France, shows that vitamin C depletion was more common among intracerebral
haemorrhage (ICH) cases than controls. The case-control study was performed on 135 subjects, with a mean plasma vitamin C concentration of 45,8 μmol/L and showed that the vitamin C level was significantly lower in 65 patients with ICH than in 65 controls. Also, the
study found that hypertension (p = 0,008), alcohol consumption (p = 0,023), and overweight
(p = 0,038) were the most important risk factors for ICH. The researchers presented that vitamin C deficiency may play a role in the aetiology of high blood pressure and may increase
the risk for atherosclerosis and heart diseases. The study reveals this vitamin contributes to
collagen biosynthesis and regulation and the deficiency of vitamin C is responsible for unstable and dysfunctional collagen which may lead to haemorrhages. The authors show that
the hospitalization length was significantly shorter for patients with a normal concentration
of vitamin C than for those with a lower level, and the risk for complication/related infe ctions was higher for those with vitamin C deficiency. (Anderson P. Low Vitamin C linked to
intracerebral haemorrhage. Medscape. February 14, 2014).
Mioara Matei
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