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REVIEW Dermatologic Signs Anatoli Freiman, Sunil Kalia, and Elizabeth A. O’Brien Background: Dermatology signs serve as important clues to primary skin disorders and internal conditions. Objective and Methods: To highlight major cutaneous signs based on a MEDLINE literature search from 1966 to March 2006. Results and Conclusions: A multitude of signs exist in dermatology. Appreciation a
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  REVIEW Dermatologic Signs Anatoli Freiman, Sunil Kalia, and Elizabeth A. O’Brien  Background:   Dermatology signs serve as important clues to primary skin disorders and internal conditions. Objective and Methods:   To highlight major cutaneous signs based on a  MEDLINE   literature search from 1966 to March 2006. Results and Conclusions:   A multitude of signs exist in dermatology. Appreciation and knowledge of cutaneous signs willenhance the care of patients with dermatologic manifestations. Ante´ce´dents:   Les signes dermatologiques sont d’importants indices de troubles cutane´s primaire et de maladies internes. Objectif et me´thodes:   Mettre en e´vidence les principaux signes au moyen d’une recherche dans  MEDLINE   sur les articles parusentre 1966 et mars 2006. Re´sultats et conclusions:   Une multitude de signes dermatologiques existe. La connaissance de ces signes ame´liorera les soinsprodigue´s aux patients pre´sentant des symptoˆmes cutane´s. ‘‘W hat is most difficult of all? It is to see with your eyes what lies in  front of your eyes’’  —  Goethe I  N THE MEDICAL LEXICON  , the term  sign   refers to anobjective physical finding observed by an examiner.Diagnosis in dermatology largely rests on the visualinspection of the skin, and certain signs serve as importantclues to primary skin disorders. With the skin being awindow to the human body, cutaneous signs can alsoindicate internal disease. Many cutaneous signs werecompiled by Al Aboud and colleagues. 1 The objective of this review is to highlight major signs in dermatology inour experience based on a  MEDLINE   literature searchfrom 1966 to March 2006. Only signs presenting as acutaneous eruption that is visible, palpable, or elicited by direct manipulation of the skin are included herein. Dermatologic Signs Albright’s dimpling sign   was described by Fuller Albright(1900–1969) and refers to dimpling over the knuckles,enhanced by clenching of the fist. 2 It results fromunderdeveloped metacarpal heads in Albright’s hereditary osteodystrophy, a syndrome characterized by short stature,a round face, a thick neck, short limbs, obesity, and shortmetacarpals. Albright’s sign is also used to refer to theshort fourth metacarpal digits observed in nevoid basal cellcarcinoma syndrome. Asboe-Hansen sign   was described in 1960 by Gustav Asboe-Hansen (1917–1989), a Danish dermatologist. 3 Thefascinating history of discovery of mechanical symptoms inblistering dermatoses was recently reviewed by Grando andcolleagues. 4 Asboe-Hansen sign is also known as blister-spread sign, which refers to the ability to enlarge a blisterin the direction of the periphery by applying mechanicalpressure on the roof of the intact blister. spreading of ablister into a clinically normal skin when lateral pressure isapplied on the edge of a blister  ; . 4 Angular blister formationis thought to be associated with intraepidermal acantho-lytic diseases (eg, pemphigus), whereas rounded blisterformation is associated with subepidermal acantholyticdiseases (eg, bullous pemphigoid). It is also observed inbullous drug eruptions. Importantly, the sign is differentfrom Nikolsky’s sign (reviewed below).Typical plaque psoriasis presents with dry, thin, silvery-white or micaceous scale.  Auspitz sign   refers to theappearance of a red, glossy surface with pinpoint bleedingon removal of the scale by scraping or scratching. Thisoccurs as a result of removal of overlying suprapapillary epithelium with subsequent rupture of dilated dermalcapillaries. Although Heinrich Auspitz, an Austriandermatologist (1835–1886), is credited for the Auspitzsign, the term is a misnomer. Both Devergie Jeune (1860) Journal of Cutaneous Medicine and Surgery JCM_2006_00042.3d  31/7/06 10:51:18 The Charlesworth Group  , Wakefield +44(0)1924 369598 -  Rev 7.51n/W (Jan 20 2003) From the Division of Dermatology, McGill University, Montreal, QC,and Division of Dermatology, University of British Columbia, Vancouver,BC.Address reprint requests to: Anatoli Freiman, MD, Division of  Dermatology, McGill University Health Centre, 687 Pine Avenue West,Room A4.17, Montreal, QC H3A 1A1; E-mail: [email protected] sympatico.ca.DOI 10.2310/7750.2006.00042   Journal of Cutaneous Medicine and Surgery, Vol 10, No 4 (July/August), 2006: pp 000–000   1  and Hebra (1845) observed this clinical sign beforeAuspitz, as did Robert Willan (1808), Joseph Plenck (1776), and Daniel Turner (1736). 5 Importantly, Auspitzsign is neither sensitive nor specific for psoriasis 6 as itoccurs in other skin conditions, including Darier’s diseaseand actinic keratosis.Named after an English surgeon, William Henry Battle(1855–1936),  Battle’s sign   occurs after fracture of the baseof the skull in the posterior cranial fossa. Bloodaccumulates beneath the fascia and causes discolorationat the mastoid process. Battle’s sign is highly specific andpredictive for the basal skull fracture. Blue dot sign   can manifest as the torsion of thetesticular epididymis and appendices. A blue or black nodule is visible under the skin on the superior aspect of the testis or epididymis. 7 The area is also usually quitetender. Butterfly sign   is characterized by erythema over themalar eminence, corresponding to the wings of a butterfly,and the nasal bridge, representing the body of thebutterfly. 8 This sign is classically described in lupuserythematosus, but it is important to differentiate it fromother causes of facial erythema, such as rosacea, seborrheicdermatitis, and erysipelas. Butterfly sign is also occasion-ally used in reference to a butterfly-shaped area of sparing observed over the upper central back, correspond-ing to the zone that is difficult to reach by hands, inconditions with severe generalized pruritus, such as atopicdermatitis. 9 Buttonhole sign   classically refers to cutaneous neurofi-bromas. It indicates the ability to invaginate the tumorinto the underlying dermal defect with digital pressure.The resulting sensation is that of inserting the finger into abuttonhole. 10 This occurs owing to the soft myxoid stomaand dermal defect caused by the protruding tumor.Buttonhole sign may also be present in syphilitic chancre;a buttonhole-like consistency is noted on the edge andbase of the ulcer on palpation. Furthermore, the sign may also be present in old pigmented nevi. Cluster of jewels sign  , also termed  string of pearls   or rosettes sign  , refers to an early stage of chronic bullousdisease of childhood, when new lesions appear at themargin of older ones, resembling a cluster of jewels. 11 Corn-flake sign   is seen in Kyrle’s and Flegel’s diseases.The polygonal irregular configuration of the lesions isquite characteristic. The lesions tend to occur over thelower extremities. Crowe’s sign  , also known as axillary freckling, is one of the defining features of type 2 neurofibromatosis.Freckling occurs in the axillae but may also be observedin other areas, such as the perineum. Crowe’s sign typically develops at a later age than cafe´ au lait macules. Cullen’s sign  , also known as  Turner-Cullen sign  , isaccredited to Thomas Stephen Cullen (1868–1953). Thesign consists of periumbical bruising, seen several daysafter subcutaneous intraperitoneal hemorrhage, which canresult from etiologies such as ruptured ectopic pregnancy and acute pancreatitis. 12 In patients with acute pancrea-titis, Grey Turner’s sign (see below) may also be seen,although both of these signs occur in only approximately 5% of cases  < . Darier’s sign   was named after Ferdinand-Jean Darier(1856–1938), a French dermatologist. 13 The sign consistsof whealing, circumferential erythema, and localizedpruritus elicited by scratching or rubbing of a lesion. Itoccurs in conditions with an increase in the number of mast cells in the dermis, including urticaria pigmentosa,systemic mastocytosis, insect bite reactions, neurofibroma, juvenile xanthogranuloma, and acute neonatal lympho-blastic leukemia.  Pseudo-Darier’s sign   is elicited whenstroking causes transient induration with piloerection andis present in several conditions, including smooth musclehamartoma and Becker’s nevus. Deck chair sign  , or papuloerythroderma of Ofuji,presents as a widespread eruption of erythematous papulesthat coalesce into rectangular plaques. The term refers tothe distinctive pattern of sparing of the natural skin folds,resembling the slats of a deck chair. 14 The sign is notspecific and has also been reported in cutaneousWaldenstro¨m’s macroglobulinemia and other condi-tions. 15 Dimple sign  , also known as  Fitzpatrick’s sign  , is a clinicalfeature used in diagnosing dermatofibromas. Lateralcompression with the thumb and index finger leads todepression of the lesion. This dimpling effect is secondary to the lesion being attached to the subcutaneous fat. Thesign may be useful in differentiating dermatofibromasfrom other lesions, including malignant melanoma.However, the sign is not completely sensitive or specificto dermatofibromas, and other diagnostic investigations,such as dermatoscopy, may help confirm the clinicalsuspicion of dermatofibroma. 16 Dirty neck sign   refers to reticulate pigmentation of theneck seen in patients with chronic atopic dermatitis. Thecondition was described in 1987 by two different groups,Manabe and colleagues and Colver and colleagues. 17,18 Thelabel ‘‘dirty neck’’ was given because of the resemblance tothe appearance of unwashed skin, with the anterolateralaspects of the neck typically affected. The pigmentary changes are secondary to melanin incontinence. 19 Journal of Cutaneous Medicine and Surgery JCM_2006_00042.3d  31/7/06 10:51:20 The Charlesworth Group  , Wakefield +44(0)1924 369598 -  Rev 7.51n/W (Jan 20 2003) 2  Freiman et al   Doughnut sign   is seen in patients with scleromyxe-dema. 20 Central depression surrounded by an elevated rimof skin is noted on the extended proximal interphalangeal joint. Drip sign   is found in dermatitis artefacta produced by corrosive liquids. Patterned burned areas correspond tothe areas of dripping of the liquid when applied by thepatient. Dubois’ sign   is shortening of the little finger associatedwith congenital syphilis. 21 This feature is seen occasionally as a late stigma of the disease. It may be associated withother stigmata of congenital syphilis, such as Hutchinson’striad (deafness, keratitis, and pointed teeth), perioralrhagades, optic atrophy, and broad-based saddleback nose. Ear lobe sign   is observed in patients who developcontact dermatitis to a substance applied with the hand tothe face and neck. Sparing of the diagonal crease of the earlobe on the ipsilateral side occurs, whereas the contral-ateral side is affected. This pattern is secondary to thehand-sweeping movement made during application of thesubstance. 22 Enamel paint sign   is seen in patients with kwashiorkor,a nutritional deficiency endemic in tropical and subtropi-cal regions. Sharply demarcated hyperpigmented desqua-mating patches and plaques resembling enamel paint occuron the skin, predominantly in areas of pressure andirritation. 23 The underlying skin is inflamed and raw. Exclamation mark hair sign   refers to the proximaltapering of hair occasionally seen in alopecia areata, wherethe dot represents the remains of the bulb. The sign is notpathognomonic for alopecia areata, and its presence may lead to misdiagnosis. 24 Flag sign   refers to horizontal alternating bands of discoloration in the hair shafts corresponding to periods of normal and abnormal hair growth. The discoloration may be reddish, blonde, gray, or white depending on thesrcinal hair color. The flag sign may be seen in patientswith nutritional deficiencies, such as kwashiorkor, andwith certain medications, such as intermittent high dosageof methotrexate or following chemotherapy. 25 Patientswith ulcerative colitis may manifest the flag sign. Forchheimer’s sign   refers to an enanthem of red maculesor petechiae confined to the soft palate in patients withrubella. The sign presents in up to 20% of patients =  duringthe prodromal period or on the first day of the exanthem. >  Frank’s sign  , srcinally described in 1973, refers to adiagonal groove across the ear lobe in adults. The sign hasbeen observed to be a marker of the coronary disease,independent of risk factors but frequently associated withthem. 26 However, more recently, Frank’s sign was reportedto have no association with coronary artery disease orretinopathy in a group of patients with type 2 diabetes. 27 Gorlin’s sign   is seen in patients with Ehlers-Danlossyndrome and is accredited to Robert James Gorlin, anAmerican oral pathologist and geneticist. It is used todescribed the ability to touch the tip of the nose with theextended tongue. Gottron’s sign   is a feature of dermatomyositis and isnamed after Heinrich Adolf Gottron (1890–1974), aGerman dermatologist. The sign refers to symmetricconfluent macular violaceous erythema that occurs overthe knuckles, hips, knees, and medial ankles. This feature isseen in 70% of patients with dermatomyositis  ? but may bealso observed in systemic lupus erythematosus. Gottron’ssign is different from  Gottron’s papules  , which are smalllichenoid hyperkeratotoic violaceous papules locatedprimarily over the interphalangeal joints of the hands. Grey Turner’s   sign is accredited to the English surgeonGeorge Grey Turner (1877–1951). The sign refers toinduration and bruising seen on the skin over thecostovertebral angle secondary to the spread of bloodfrom the anterior pararenal space. The condition iscommonly associated with acute hemorrhagic pancreatitisand other causes of retroperitoneal hemorrhage. 28 Groove sign   is classically noted in heterosexual maleswith lymphogranuloma venereum. 29 The term refers to theinflammatory mass of femoral and inguinal nodesseparated by a depression or groove made by Poupart’s(inguinal) ligament, which occurs in 20% of affected men.  @ Hair collar sign   is an important cutaneous marker forneural tube closure defects of the scalp. 30 The sign consistsof a ring of dark coarse hair surrounding a malformation,such as aplasia cutis, encephalocele, meningocele, orheterotropic brain tissue. The defect is often in themidline, and the occipital or parietal scalp is typically affected. Hanging curtain sign   is seen in patients with pityriasisrosea. 31 When the skin is stretched across the long axis of the herald patch, the scale is noted to be finer, lighter, andattached at one end, which tends to fold across the line of stretch. Heliotrope sign   is seen in patients with dermatomyositisas a violaceous erythema involving the periorbital skin. 32 The term refers to the purplish color of the flowers of theheliotrope plant, so named because its flowers rotate toface the sun. Similar to Gottron’s sign, the heliotrope signis strongly suggestive of dermatomyositis. Hertoghe’s sign  , also known as madarosis, is character-ized by the lack of the outer third of the eyebrows. Duringthe 1980s, Hanifin and Rajka included Hertoghe’s sign as Journal of Cutaneous Medicine and Surgery JCM_2006_00042.3d  31/7/06 10:51:20 The Charlesworth Group  , Wakefield +44(0)1924 369598 -  Rev 7.51n/W (Jan 20 2003) Dermatologic Signs   3  part of the minor criteria for diagnosing atopic dermatitis. A However, the validity of these criteria has been subse-quently debated. The differential diagnosis of Hertoghe’ssign includes atopic dermatitis, trichotillomania, ectoder-mal dysplasia, alopecia areata, alopecia mucinosa, leprosy,syphilis, ulerythema ophryogenes, systemic sclerosis, andhypothyroidism. It can also sometimes be seen in normalelderly patients. Hoagland’s sign   is early and transient bilateral upper lidedema occurring in patients with infectious mononucleo-sis. The sign is usually present only for the first few days of the clinical presentation of the illness. Hoagland alsodescribed other criteria important for diagnosing infec-tious mononucleosis. 33 Holster sign   is found in dermatomyositis. Pruritic,macular, violaceous erythema affects the lateral aspects of hips and thighs.Sir Jonathon Hutchinson (1828–1913) was a renownedEnglish surgeon, whose name is accredited to many signsand eponyms.  Hutchinson’s nail sign   was first described in1886 and refers to periungual extension of brown-black pigmentation onto the proximal and/or lateral nail folds.The presence of Hutchinson’s sign should raise thesuspicion of subungual melanoma; however, the sign isneither highly specific nor sensitive.  Pseudo-Hutchinson’s sign   represents the presence or illusion of pigment in theperionychium and can be associated with a variety of disorders. 34 Kawabata and colleagues examined 6 sub-ungual melanomas in situ and 18 subungual melanocyticnevi and compared pigmentation of the nail plates andhyponychium with the use of a dermatoscope. 35 Hutchinson’s sign on the hyponychium was not alwaysevidence of subungual melanoma; however, a widedifference was observed in dermatoscopic features, sug-gesting that dermatoscopy can help with the diagnosis of subungual melanoma. 35 Hutchinson’s nose sign   refers to the presence of vesiclesoccurring on the tip of the nose in patients with herpeszoster. This presentation indicates that the nasociliary branch is affected and that eye involvement may be presentor forthcoming; therefore, an ophthalmologic assessmentis necessary for these patients. However, some believe thatthis association is not as strong as once believed. 36  Jellinek’s sign   refers to eyelid pigmentation occasionally seen in hyperthyroidism. The hyperpigmentation issecondary to increased corticotrophin levels and may alsooccur on other areas of the face but usually spares thebuccal mucosa. Leser-Tre ´ lat sign  , also known as eruptive seborrheickeratosis, is accredited to two European surgeons, EdmundLeser (1853–1916) and Ulysse Tre´lat (1828–1890). Thesign is defined as the sudden eruption of multipleseborrheic keratoses, which are often pruritic, and isclassically associated with internal malignancy. 37 Adenocarcinomas are typically reported, particularly of the stomach 38 and colon but also of the breast, uterus,esophagus, and pancreas. Other reported associationsinclude lung cancer, 39 melanoma, 40 and mycosis fun-goides. 41 Because both seborrheic keratoses and cancer areprevalent in the elderly, the validity of Leser-Tre´lat sign hasbeen questioned. 42 An association with malignantacanthosis nigricans has been proposed as one of thefeatures that support the legitimacy of the sign as aparaneoplastic marker. 43 Besides acanthosis nigricans,other signs of malignancy may occur with Leser-Tre´latsign, including acquired hypertrichosis, tylosis, floridcutaneous papillomatosis, and acrokeratosis of Bazex. Muehrcke’s sign   refers to paired, transverse, narrowedwhite bands that run parallel to the lunula of the nails andare seen in patients with hypoalbuminemia or thosereceiving chemotherapy agents. They occur usually on thesecond, third, and fourth fingernails but not on thethumbnail. The distal band tends to be wider than theproximal band. Conditions resulting in Muehrcke’s signthat are associated with hypoalbuminemia include nephro-tic syndrome, glomerulonephritis, liver disease, andmalnutrition.In patients with scleroderma, ridging and tightening of the neck skin can form a visible and palpable tight bandthat lies over the platysma in the hyperextended neck. 44 Itis referred to as  neck sign   but should not be confused withBrudzinski’s sign, which is seen in patients with meningitisand is also referred to as neck sign. Necklace of Casal sign   refers to hyperpigmentationoccurring on the neck owing to pellagra. The ‘‘necklace’’can extend as a broad collar-like band around the entirecircumference of the neck. 45 Sometimes the necklaceextends anteriorly over the sternum to the level of thenipples and ends in a point or square. Cutaneous changesin pellagra appear primarily on sun-exposed areas on theneck, face, and dorsal parts of the hands, arms, and feet,but patients usually also have dermatitis elsewhere. Nikolsky’s sign   was srcinally initially described in 1896by Peter Vasiliyevich Nikolsky, a Russian dermatologist(1858–1940), in patients with pemphigus foliaceus. Thesrcinal statement highlighted two methods in manifestingthe sign: ‘‘by pulling the ruptured wall of the blister it ispossible to take off the horny layer for a long distance on aseemingly healthy skin’’ and ‘‘the rubbing off of theepidermis between the bullae by slight friction without Journal of Cutaneous Medicine and Surgery JCM_2006_00042.3d  31/7/06 10:51:20 The Charlesworth Group  , Wakefield +44(0)1924 369598 -  Rev 7.51n/W (Jan 20 2003) 4  Freiman et al 
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