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Report

A clinical approach to diagnose patients with localized


telangiectasia
Ruchi Gupta1, MD, Ram Krishan Gautam1, MD, DVD, MNAMS, Minakshi Bhardwaj2, MD,
and Amrita Chauhan1, MD

1
Department of Dermatology STD & Abstract
Leprosy, and 2Department of Pathology, Telangiectasia, or dilated blood vessels, may represent a benign condition or a marker of a
P.G.I.M.E.R. and Dr Ram Manohar Lohia
much more serious internal or cutaneous malignancy (e.g. mycosis fungoides). They can
Hospital, New Delhi, India
be generalized or localized in distribution. ‘Localized telangiectasia’ can be macular or
Correspondence papular. Macular ones can be further divided into two major categories: primary and
Ruchi Gupta, MD secondary. They can occur on their own (primary), after skin injury (e.g. sun damage, post-
Senior Resident radiation therapy, after prolonged topical steroid application), or may arise due to an
Department of Dermatology STD & Leprosy
underlying condition (secondary). While telangiectases can spring from a multitude of
P.G.I.M.E.R. and Dr Ram Manohar Lohia
Hospital
possible causes, the location of the lesions, in combination with a careful history and
Baba Kharag Singh Marg, exmination, often helps in elucidating the correct diagnosis. A patient with localized
New Delhi 110001 telangiectasia as a manifestation of malignancy may be difficult to diagnose, however the
India diagnosis is one of exclusion, and a thorough evaluation should be performed before
E-mail: ruchi85mon@gmail.com
diagnosing this condition. This article reviews possible conditions to consider in these
patients and suggests an approach to their evaluation.
Conflicts of interest: None.
Funding support: None.

adenopathy. The laboratory findings, including basophils


Introduction
in the peripheral blood smear, liver transaminases, alka-
One of the difficulties dermatologists encounter when line phosphatase, serum estradiol, and thyroid hormones,
attempting to diagnose conditions with localized telangi- were within normal limits. Suspecting the possibility of
ectasia is where to start. Faced with such a patient, it is unilateral nevoid telangiectasia (UNT), telangiectasia
helpful to have a systematic approach rather than simply macularis eruptiva perstans (TMEP), or morphea, we per-
thumb through the books. We hereby present a case with formed a skin biopsy, which showed dilated thin-walled
unilateral dermatomal telangiectasia with an approach to capillaries with mild perivascular inflammatory infiltrate
categorize and diagnose such cases. comprised of lymphocytes and spindle-shaped toluidine
blue-positive mast cells (Fig. 2). There was no remarkable
sclerosis in the dermis. Thus, a diagnosis of TMEP was
Illustrative case
made.
A 31-year-old woman presented with spontaneous erup-
tion of asymptomatic, red–tan spots on the inner side of
Discussion
her left arm during her immediate postpartum period.
There were no systemic features. She did not have any Telangiectasias are defined as visibly dilated blood vessels
family members with similar skin lesions. On examina- in the skin. Most commonly, they appear on the skin and
tion, multiple brownish erythematous macules (2–6 mm mucous membranes as small red linear markings. Ultra-
in diameter) with telangiectasias were seen arranged line- structurally, telangiectasias are not vascular proliferations
arly over the medial aspect of the left arm, involving an but are caused by dilations of pre-existing vessels, which
approximately 10 cm long area in the distribution of the include either capillaries or venules.1 Capillary telangiec-
intercostobrachial nerve (T2 dermatome) extending to tasias appear red or pink and are usually less than
involve the lateral wall of the axilla (Fig. 1). The lesion 0.2 mm in diameter, unlike venous telangiectasias, which
blanched on diascopy but did not urticate or itch after a usually appear more blue in color and are greater than
brisk stroke. There was no hepatosplenomegaly or lymph- 0.2 mm in diameter. Capillaries are usually bilateral and
e294

International Journal of Dermatology 2015, 54, e294–e301 ª 2015 The International Society of Dermatology
Gupta et al. Diagnosing patients with localized telangiectasia Report e295

(a)

(b)

Figure 1 Multiple red tan macules (2–6 mm in diameter)


arranged linearly over medial aspect of left arm, in the
distribution of intercostobrachial nerve (T2 dermatome)

are symmetrically distributed on the skin. When they are


numerous enough to become confluent, the skin appears
diffusely erythematous, and discerning individual telangi-
ectasias becomes impossible.
Morphologically they can also be broadly divided into
two groups: (a) macular, which may be further subdi-
vided into linear (e.g., most commonly visible over ala of
nosa), arborized or Besenreiser type (e.g., on thigh), spi-
der or star-like, and punctiform type; and (b) papular
(e.g., cherry angioma, angiokeratoma, etc.). Braverman
Figure 2 (a) Multiple dilated thin-walled capillaries with
and Ken-Yen performed ultrastructural analyses of telan-
mild perivascular inflammatory infiltrate in papillary dermis
giectasias in various disorders by light and electron (hematoxylin and eosin stain, 940 magnification). (b)
microscopy and found that macular telangiectasias are Spindle-shaped toluidine blue positive mast cells in
produced by dilatation of postcapillary venules of the perivascular location (toluidine blue stain; 9100
upper horizontal plexus, whereas papular telangiectasias magnification)
are produced by spherical and tubular dilatations of capil-
lary loops in dermal papillae.2 nation, often helps in elucidating the correct diagnosis.
In this review, we will focus only on superficial macu- Notably, the presence or absence of atrophy in lesional
lar telangiectasia in a localized distribution. As a signifi- skin helps to narrow down the clinical diagnosis further.
cant group of disorders present with superficial macular Eventually, in doubtful cases, skin biopsy is the tool to
telangiectasias in a localized and/or dermatomal distribu- reach the final verdict.
tion, there is a need for an approach to categorize and
diagnose such cases (Fig. 3). From a pathophysiological Primary localized telangiectasia without skin atrophy
point of view, macular telangiectasias are divided into The differential diagnosis engendered by primary local-
two major categories: primary and secondary. They can ized telangiectasia without skin atrophy is broad and
occur on their own (primary), after skin injury (e.g., sun encompasses disorders, such as UNT, spider nevi, costal
damage, post-radiation therapy, after prolonged topical fringe, telangiectasia associated with HIV, angel’s kiss,
steroid application), or may arise due to an underlying stork bite, angioma serpiginosum, and rarely nevus
condition (secondary). While telangiectasias can spring flammeus. In unilateral nevoid telangiectasias, which were
from a multitude of possible causes, the location of the the initial primary diagnostic consideration in our patient,
lesions, in combination with a careful history and exami- there are patches of superficial telangiectasias in a unilat-

ª 2015 The International Society of Dermatology International Journal of Dermatology 2015, 54, e294–e301
e296 Report Diagnosing patients with localized telangiectasia Gupta et al.

Localized macular telangiectasia

Primary (not associated with Secondary (when


any other distinct primary telangiectasias are one of
disease) the features of a
distinct primary
disease)

Associated with Without skin


skin atrophy atrophy Unilateral
nevoid
Without atrophy With atrophy
telangiectasia
Brocq’s telangiectasias In relation to high Yes
Spider nevi Connective tissue disease:
estrogenic states Rosacea
Purpura annularis No - Scleroderma
telangiectodes of - Telangiectoid variant of
Majocchi Mastocytosis DLE
(TMEP)
Elderly age group Childhood and adolescence Poikiloderma of Civatte
Seborrheic (due to actinic damage),
Costal fringe Involve upper half dermatitis
-CM (Stroke bite, Poikiloderma atrophicans
Angel’s kiss, Nevus vasculare (CTCL)
HIV-associated flemmeus) Hereditary
telangiectasias hemorrhagic
Angiolupoid
telangiectasia
sarcoidosis
Involve lower half
Post treatment:
-Angioma
- Steroid application
serpiginosum - Radiation therapy

Figure 3 An approach to a patient with localized macular telangiectasia. CM, capillary malformation; CTCL, cutaneous T-cell
lymphoma; DLE, discoid lupus erythematosus; TMEP, telangiectasia macularis eruptiva perstans

eral dermatomal or linear distribution that can be con- tion. Occurrence in a dermatomal pattern has been
genital or acquired. The underlying mechanism is believed reported.6
to be somatic mosaicism, which is unmasked by a sys- The costal fringe consists of a band-like pattern of
temic increase in estrogen levels exhibited during preg- venous telangiectasias along the anterolateral costal mar-
nancy, puberty, and alcoholic cirrhosis.3 The literature gins (Fig. 4). It is an easily recognized entity, usually seen
includes reports of UNT associated with hyperthyroid- in elderly men. Association with an underlying disease is
ism,4 while other cases showed no associated abnormali- not well established. Sartori et al.7 examined 1523 young,
ties.5 Dermatomes C3–D1 are the most commonly seronegative, active duty air force personnel (1203 men
involved sites.3–5 Histologically, there are multiple and 320 women) between the ages of 17 and 34 years.
dilated, thin-walled vessels in the papillary and upper The costal fringe was present in only three men (0.2%).
reticular dermis with notable absence of mast cells. Our They concluded that the costal fringe is a rare finding in
patient fulfilled all clinical criteria of UNT, i.e., multiple healthy young adults. On the other hand, linear telangiec-
blanching telangiectasias primarily in a T2 dermatomal tasias in a broad, crescent-like distribution across the
distribution in a young female during the postpartum per- chest are a relatively common finding in homosexual men
iod. If fewer spindle-shaped mast cells were seen on tolui- and are significantly, although not exclusively, associated
dine blue staining, we could have diagnosed our case as with HIV infection.8 Leg veins encountered in the early
UNT. stage of chronic venous disease is an important differen-
Spider nevus is another common telangiectatic condi- tial of venous telangiectasias, i.e., C1 stage of venous dis-
tion frequently associated with a high estrogenic state. It ease of legs as per CEAP (Clinical severity, Etiology,
is usually seen in pregnancy and is frequently associated Anatomy, and Pathophysiology) classification. Superficial
with liver disease but may be encountered in up to 15% spider veins (reticular veins) are seen over the lower leg
of normal people. An arcade of vessels radiating out from in this condition. At this stage, the telangiectasias can be
a central arteriole is the most characteristic clinical fea- managed with non-surgical modalities such as the intense
ture. The upper half of the body, especially the face, pulsed light system (IPLS). A few studies have reported
neck, upper chest, and hands, is the usual site of predilec- the successful use of IPLS for the treatment of leg telangi-

International Journal of Dermatology 2015, 54, e294–e301 ª 2015 The International Society of Dermatology
Gupta et al. Diagnosing patients with localized telangiectasia Report e297

dermis is consistent with the propensity of lesions to


become papular. The colloquial differentials are progres-
sive pigmentary purpuric diseases. In Schamberg disease,
the so-called cayenne pepper spots are macules that tend
to coalesce and form diffusely pigmented patches,
whereas purpura annularis telangiectodes of Majocchi,
although bilateral, resemble more closely due to the
occurrence of telangiectatic macules that enlarge peripher-
ally to form small rings (discussed below).

Primary telangiectasia with skin atrophy


Only a few disorders with primary telangiectasia present
with skin atrophy. They include purpura annularis telan-
Figure 4 Band-like arrangement of venous telangiectasias giectodes of Majocchi and Brocq’s telangiectasias. Pur-
over chest pura annularis telangiectodes of Majocchi, most
commonly seen in adolescents, is characterized by sym-
ectasias ranging in size from 0.1 to 3 mm in diameter. metrical, purpuric, telangiectatic annular patches and pla-
Green9 reported complete clearance of leg telangiectasias ques with skin atrophy, with a predilection for the lower
in 10% of patients, partial clearance in 25% patients, extremities and buttocks. The presence of skin atrophy
and no improvement in another 56% of patients with and purpura (do not blanch with pressure) clinically and
IPLS. On the other hand, Goldman and Eckhouse10 perivascular inflammatory infiltrate with extravasation of
reported 75–100% clearance of telangiectasias in 79% of erythrocytes histologically, differentiate it from angioma
treated patients and better than 50% clearance in 94% of serpinginosum. Although primarily annular, these patches
cases. A very low rate of adverse effects was reported. may be linear, stellate, or serpiginous in shape.13
Capillary malformations (CMs), visible as telangiectatic Brocq’s telangiectasias are essential localized telangiec-
macules, occur in up to 40–50% of newborns. They fade tasias on a sclerodermiform background. Their nosologi-
progressively during infancy and are therefore termed as cal place is not clear among the essential telangiectasias;
fading macular stains. Some CMs, particularly those on morphologically they seem to be quite similar to poikilo-
the nape of neck (stork bite) and rarely on the glabellar derma atrophicans vasculare but without any discernable
region (angel’s kiss), persist into adulthood and are underlying cause.14
termed medial telangiectatic nevus. They can be easily
recognized by their typical location and history of pres- Secondary telangiectasia with skin atrophy
ence since birth. Nevus flammeus may occur on any part When associated with atrophy, telangiectasias are usually
of the body but commonly affects the face in the distribu- secondary to either connective tissue diseases (sclero-
tion of the trigeminal nerve. Initially, the lesions are tel- derma and telangiectoid variant of discoid lupus erythe-
angiectatic macules, but with time they may mature into matosus), as a component of poikiloderma atrophicans
violaceous plaques; however, they may remain static as vasculare (PAV), or rarely as a variant of sarcoidosis
macular stain in 60% of cases.11 known as angiolupoid sarcoid. Telangiectasia (mat-like
The aforementioned conditions are seen most com- broad macules that are polygonal in shape and 1–2 mm
monly above the waist area. Angioma serpiginosum is a across) occurring primarily on the hands and face are a
rare unilateral disorder of the superficial blood vessels prominent feature in scleroderma. They are present in the
affecting areas below the waist (lower limb or buttock), majority of patients in association with loss of cutaneous
with female predominance. It usually arises in childhood elasticity and hardening of the skin (sclerosis). These
and then progresses for a year or more. It is typically seen changes represent microvascular and fibrous changes
as multiple pinpoint, red macules, which have a tendency inherent in the scleroderma disease process, respectively.15
to become papular. They occur in groups, which enlarge Mould and Roberts-Thomson studied the correlation
via the eruption of new lesions at the periphery, while between the amount of telangiectasia in scleroderma with
those at the center involute. In this manner, small rings disease duration and found a significant correlation, par-
or serpiginous patterns are formed. The palms, soles, and ticularly in the limited subtype; on the other hand, no
mucous membranes are spared. Rare bilateral cases with correlation was observed between the number of telangi-
extensive cutaneous involvement are seen, but most cases ectasias with disease duration or nail-fold capillary diam-
are unilateral.12 Histologically, the presence of dilated eter in diffuse scleroderma or systemic sclerosis.16
and tortuous capillaries in the dermal papillae and upper Although mat-like telangiectasias arise from dilatation of

ª 2015 The International Society of Dermatology International Journal of Dermatology 2015, 54, e294–e301
e298 Report Diagnosing patients with localized telangiectasia Gupta et al.

post-capillary venules, sometimes they may involve dilata- a case of PAV, the spectrum of investigations should
tion of dermal capillaries leading to diffuse erythematous include tests for any underlying systemic disease, lym-
appearance, and thence clinicians should be aware that phoma, or connective tissue disorder.23 Old age and
an apparent acquired PWS may be an early manifestation refractoriness to treatment should raise the suspicion of
of localized morphea.17 premalignant PAV. When no underlying condition is
In 1888, Radcliffe Crocker18 first described a telangiec- found on multiple skin biopsies, the condition is labeled
tatic form of lupus erythematosus characterized by sym- as sclerodermiform plaque-like essential telangiectasias or
metric persistent circumscribed patches on both cheeks, Brocq’s telangiectasias. Recently, an etiological classifica-
which on palpation were decidedly thickened and shot tion with the key differentiating features for each individ-
through with dilated blood vessels. The extensor surface ual cause, to help in making a precise diagnosis of
of the hands was the seat of patchy persistent erythema, different causes and a step-by-step approach to the man-
resembling chilblain, which after involution showed atro- agement of patients with acquired poikiloderma, has been
phic scarring. According to Crocker, the patches on the described in detail in the literature.24
cheek simulated the red paint on a clown’s face. Under Sarcoidosis is a multisystem granulomatous disorder
the term erysipelas perstans faciei, Kaposi,19 in 1872, also with protean manifestations ranging from self-limited skin
brought attention to the deep red patches on the face lesions to intractable organ failure. Among the protean
with purpura preceding the onset of lupus erythematosus manifestations of cutaneous sarcoidosis, including macu-
acutus disseminatus. Lupus erythematosus telangiectoides lopapules, nodules, plaques, subcutaneous nodules, infil-
is a variant of disseminated discoid lupus erythematosus, trative scars, and lupus pernio, the angiolupoid
characterized by a persistent, blotchy, reticulate telangiec- sarcoidosis is a rarely reported variant characterized by
tasia, which occurs on the face, neck, ears, dorsa of the erythematous plaques with superficial telangiectasia on
hands, breasts, heels, and on the sides of the feet.20 Cases the face, particularly in paranasal areas. It results in
with localized lesions are on record.21,22 Other disorders severe disfigurement and can cause profound social
with telangiectasia on the face such as rosacea, carcinoid, embarrassment. Since its first description in 1913, only a
seborrheic dermatitis, hereditary hemorrhagic telangiecta- few cases had been reported in the English language liter-
sia (history of oro-nasal bleed and involvement of ature.25 Tsai et al.26 reviewed the dermatological files in
mucosa), and bloom syndrome (history of photosensitivi- Chang Gung Memorial Hospital over 16 years and found
ty) may be differentiated by the absence of skin atrophy. only eight cases with consistent features of angiolupoid
Facial telangiectasia due to prolonged steroid application sarcoidosis. They suggested that angiolupoid sarcoidosis
(history of topical application of high potency steroid) is a rare but real variant of sarcoidosis. Interestingly, the
and angiolupoid sarcoidosis can be differentiated by clas- incidence of pulmonary and ocular involvement is report-
sical histologic findings. The histology of this type of edly low.26–28 However, more cases are needed to con-
lesion shows an atrophic epidermis, with dilatation of the firm the optimistic conclusions. In spite of being
superficial vessels of the skin and slight infiltration of the asymptomatic, treatment of angiolupoid sarcoidosis is
papillary part of the corium. Vacuolization of basal cells imperative due to the severe disfigurement disturbing the
and thickening of the basement membrane helps in mak- patients. Although diverse methods of treatment have
ing the diagnosis. been tried, including the systemic, topical, and intrale-
Poikiloderma is a morphologic and descriptive term sional glucocorticoids, doxycycline, hydroxychloroquine,
referring to a combination of cutaneous atrophy, telangi- and antituberculosis agents, none of them are definitive.
ectasia, and varied macular pigmentary changes that The differential diagnosis of angiolupoid sarcoidosis
result in a mottled skin appearance. Its etiology includes includes lupus pernio, chilblain lupus erythematosus, and
both congenital and acquired causes. PAV is characterized mycobacterial (including leprosy) and fungal infections.
by one or a limited number of patches (composed of tel- Hitherto, the natural progression of lesion along with the
angiectasia, atrophy, and hyper/hypopigmentation) espe- histopathological features is of utmost importance in
cially over the breasts or buttocks (limb girdle area). It making one diagnosis over another. Lupus pernio charac-
may be an idiopathic disorder or a manifestation of con- teristically involves the tip of the nose, does not show any
nective tissue diseases (lupus, dermatomyositis, sclero- tendency of resolution, and is associated with severe pul-
derma), lymphomas (parapsoriasis en plaques and monary involvement. Angiolupoid variant, on the other
mycosis fungoides), and genodermatoses (Rothmund– hand, is distinctive with predominant involvement of the
Thomson syndrome, hereditary sclerosing poikiloderma, cheeks and relative absence of systemic involvement. In
dyskeratosis congenita). Other causes include physical addition, the presence of multiple dilated blood vessels
trauma (radiodermatitis, burns, freezing) and certain in the papillary dermis in addition to paucilymphocytic
ingested substances such as arsenic compounds. Hence, in non-caseating granulomas is enough to differentiate it

International Journal of Dermatology 2015, 54, e294–e301 ª 2015 The International Society of Dermatology
Gupta et al. Diagnosing patients with localized telangiectasia Report e299

from other granulomatous diseases. Similarly, chilblain skin, and mucous membranes often rupture and bleed
lupus and infectious causes can be easily differentiated by after slight trauma. The most common clinical manifesta-
the presence of hydropic degeneration of basal cells and tion is spontaneous and recurrent nosebleeds (epistaxis)
the infectious organisms, respectively. beginning on average at age 12 years.33
Topical corticosteroid-induced rosacea-like dermatitis
(TCIRD) is an entity that starts after discontinuing potent
Conclusion and recommendations
topical corticosteroid after its application for a consider-
able time. It is a rebound phenomenon, which usually As even benign-looking telangiectasias can be a marker of
appears on the face in a perioral, diffuse, and centrofacial underlying systemic disease and result in profound disfig-
distribution. It may or may not be associated with skin urement, picking the correct diagnosis out of the basket
atrophy. The majority presents with a history of exacer- requires a systematic approach. When associated with
bation of symptoms after sun exposure, most probably skin atrophy, most telangiectasias are secondary in origin.
due to atrophy and vasodilatation of the facial skin. Inter- Although history and location of lesion are usually help-
estingly, eye problems are reportedly absent.29 Treatment ful in elucidating the correct diagnosis in disorders with
involves a fine balance between gradual tapering to com- primary telangiectasia, most secondary telangiectasias
plete cessation of the topical steroid and addition of oral require a skin biopsy for final confirmation. Patients with
anti-inflammatory antibiotics and/or topical antibiotics. potentially more serious conditions such as PAV need
observation and multiple biopsies before the diagnosis of
Secondary telangiectasia without skin atrophy cutaneous T-cell lymphoma is ruled out.
Conditions such as TMEP, rosacea, carcinoid, seborrheic Although treatment results may not be permanent for most
dermatitis, and hereditary hemorrhagic telangiectasia of these cases, for cosmetically sensitive areas of the body,
(HHT) present with linear telangiectasia on the face with- gentle cautery can be used for a small number of lesions.
out any skin atrophy. TMEP is a rare form of cutaneous Laser therapy is also an effective treatment and can be useful
mastocytosis characterized by multiple symmetrically in those having a larger number of lesions. We treated our
scattered telangiectatic macules primarily involving the patient with pulsed dye laser (585 nm, at 2 maximum) for
trunk, extremities, or face. Histologically, minimal mono- three months, but it failed to improve her eruptions.
nuclear infiltrate, containing mast cells around the capil-
laries, are characteristic. Special stains, such as Giemsa or
Multiple choice questions
toluidine blue, highlight the presence of mast cells, reveal-
ing their metachromatic cytoplasmic granules. Unilateral 1 Macular telangiectasias most commonly arise from
TMEP over the face30,31 and breast32 have been reported which part of the cutaneous vasculature
previously, and to our knowledge, the illustrated case of a Capillary
linear unilateral TMEP involving the lateral wall of the b Postcapillary venules
axilla (T2 dermatome) in this review has never been c Small collecting veins
reported. In such unusual cases, it is all the more important d Precapillary arterioles
to have a systematic approach to avoid misdiagnosis. 2 All of the following conditions mostly involve above
Association with flushing and systemic symptoms such the waist area except
as diarrhea should raise the suspicion of carcinoid syn- a Acquired nevoid telangiectasia
drome, which is seen in 5% of cases with carcinoid b Stork bite
tumors of the gastrointestinal tract. Rosacea usually has a c Angioma serpinginosum
typical unmistaken distribution and morphology. Associa- d Costal fringe
tion with dandruff and yellow greasy scales are a pointer 3 In which of the following conditions are telangiectasias
towards seborrheic dermatitis. Similarly, telangiectasia are associated with skin atrophy?
mainly over the lips and oral mucosa and sometimes on a Purpura annularis telangiectoides
the face and dorsum of the hands in association with a b Rosacea
nosebleed are seen in HHT. It is characterized by the c Brocq’s telangiectasia
presence of multiple arteriovenous malformations. d Spider nevi
Although HHT is a developmental disorder, caused due 4 All of the following are true about telangiectasia mac-
to mutation in germline genes, endoglin, and ALK-1, ularis eruptiva perstans except
infants are occasionally affected. In most people, the fea- a Most common form of cutaneous mastocytosis
tures are age-dependent, and the diagnosis is not sus- b Characterized by red tan macules less than 0.5 cm
pected until adolescence or later. Small arteriovenous in diameter
malformations (telangiectasias) close to the surface of the c Most common site of involvement is upper trunk

ª 2015 The International Society of Dermatology International Journal of Dermatology 2015, 54, e294–e301
e300 Report Diagnosing patients with localized telangiectasia Gupta et al.

d Skin biopsy is diagnostic 4 Kavak A, Kutluay L. Unilateral nevoid telangiectasia and


5 Telangiectasias associated with high estrogenic states hyperthyroidism: a new association or coincidence? J
are seen in_______? Dermatol 2004; 31: 411–414.
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