Skin is the largest body organ providing protective covering to the underlying structures. It is thin and more delicate in children. Over 10 per cent of children reporting to the primary physician have a dermatologic disorder. Skin manifestations may occur due to underlying primary skin disorder or they may represent manifestations of a systemic disorder. A number of viral exanthems are limited to children. A detailed examination of skin and its appendages is required when primary manifestations of a disease process are limited to skin.


Apart from demographic details, enquiry should be made regarding the duration of skin lesions, involvement of initial site and their subsequent progression, evolution and distribution. The specific areas of the skin surface involved, whether predominantly over the extensor surfaces or flexor creases should be noted. The presence of itching, irritation and smarting sensation should be asked. Infants manifest itching by irritability and restlessness.

SKIN AND ITS APPENDAGES The presence of associated constitutional symptoms like fever, joint pains, abdominal pain, inborn error of metabolism or any other systemic manifestations should be looked for. Skin manifestations may occur due to deficiency of essential nutrients and trace elements like vitamins, zinc and essential fatty acids. History of drug intake and possibility of an adverse drug reaction should always be kept in mind. Administration of sera, blood and blood components should be asked to exclude serum sickness and graft-versus-host reaction. A detailed probing is required to elicit history of contact with offending cosmetic agent, poison ivy or plant, insects (mosquitoes, ants, honey bees, centipede, scorpion etc.), and animals (fleas, visceral larva migrans, cat scratch disease etc). History of similar manifestations among household contacts is suggestive of an infective disorder like viral infection, pyoderma and scabies. Family history of eczema, atopic dermatitis, autoimmune disorder and psoriasis etc. should be enquired. Exclude systemic manifestations by a detailed review of body systems. A detailed history of topical and systemic therapy taken should be recorded.

Physical Examination

Examination of skin must be conducted in a well-lighted room preferably with optimal sunlight. Magnifying glass should be used to study the morphology of skin lesions. It is desirable to completely undress the young child while older children can have a loose fitting gown. The presence of constitutional manifestations like fever, toxemia, anorexia and systemic symptoms demand a detailed physical examination. Vital signs should be checked in children with generalized skin disorder. All areas of skin including palms, soles, creases, scalp and anogenital skin should be scrutinized. Because of ectodermal origin of both skin and CNS, many genetic or developmental defects of skin are associated with CNS malformations or hamartomas.

Spider nevi, palmar erythema, gynecomastia and xanthomas may be seen in patients with chronic liver disease with hepatocellular failure. Mucous membranes, hair, and nails are often involved in various skin disorders and should be examined in detail. The most important aspect of the physical examination of skin is the morphology of individual skin lesions. In addition to thorough inspection of skin, palpation of skin lesions may allow the examiner to appreciate subtle depression or elevation of skin lesions. The following morphologic features of skin lesions should be carefully looked for and recorded on a human diagram for their extent and distribution. A number of viral exanthems can be diagnosed clinically by characteristic distribution and evolution of skin rash.

Characteristics of skin rash in common viral exanthems
Skin rash appears after 3-4 days of prodotnal features of fever, coryza and conjunctival congestion The fever shoots up on the day of onset of rash. Maculo-papular or morbilliform confluent rash starts behind the ears and spreads to the forehead, face, neck, trunk and extremities. Koplik spots (grayish-white dots like grains of sand with reddish areola starting over buccal mucosa opposite lower molars) which appear 24 hours before or 24-48 hours after the onset of rash are characteristic early marker of measles. The rash starts to fade from the face on the third day and continues to disappear in the order of its appearance. When eruption fades, brownish coppcr discoloration of skin with powdery desquamation is seen tor several days.
Characteristics of skin rash in common viral exanthems (Contd.)
Rubella (German measles)
The rash appears after 1 -2 clays of mi Id prodrome of fever, cough and coryza. The exanthem begins on the face and extends over the body within a few hours as fine, light-pink discrete macules or scarlatiniform rash. Suboccipilal and posterior auricular lymphnodes may be slightly enlarged and tender. The rash begins to fade after 2 to 4 days leaving behind fine desquamation. It is difficult to differentiate rubella from mild measles modified by prior immunily or immunization.
Chicken pox
There is no prodrome or mild symptoms of upper respiratory catarrh for one to two days. Rash appears in crops over the trunk with simultaneous appearance of macules, papules, vesicles (like dew-drops or tear drops) which progress to develop pustules and crusts. Lesions spread to peripheral areas involving extremities and face . Pruritis is common. The crops of new lesions continue to appear over 4 to 5 days and exanthem lasts up to 8 to 14 days. Most lesions heal without scarring unless there is super added bacterial infection. When all the lessions are crusted, the patient is no longer contagious.
Erythema infectiosum (fifth disease)
It is caused by parvovirus B19 and manifests as bright red confluent rash over the cheeks, malar prominence and nose giving an appearance of “slapped-face”. Circum-oral pallor may be present. Erythematous macules may spread over the lateral and extensor aspects of extremities, trunk and buttocks. During recovery there is characteristic lace-like or reticular pattern due to central clearing of erythematous macules.
Characteristics of skin rash in common viral exanthems (Contd.)
Roseola infantum (exanthum subitum)
The onset is sudden with high grade fever at times with convulsions. Coryza is mild or absent. The fever falls by crisis after 3-4 days followed by maculo-papular skin eruption starting on the trunk and involving arms and neck. The rash is absent or minimal on the face or legs. The skin rash fades within 24 hours without any desquamation.
Hand foot and mouth disease
It is usually caused by coxsackie A16 and other coxsackie viruses. There is sore throat with oral ulcerations due to vesicles. Painful papulo-vesicular lesions appear over the hands and feet.
Infectious mononucleosis
There is a bright red morbilliform or scarlatiniform skin rash which is often precipitated by intake of ampicillm. The .course is prolonged with associated cervical lymphadenopalhy, herpangina (sore throat), mild jaundice and splenomegaly.
Coxsackie viruses A9 and B5 and echoviruses 4, 9 and 16 may produce maculopapular, morbilliform, urticarial or petechial skin rash. There are no characteristic or diagnostic clinical features.
Nonspecific maculopapular eruption is often associated with adenovirus infection.

Primary Lesions

Primary skin lesions provide the most vital clues for making a correct diagnosis. They are the most representative lesions of the disease process without any alteration by the patient by scratching, rubbing, secondary infection or therapy.

Macules. They are flat, nonpalpable areas of color change of skin. Macules may be erythematous, hypopigmented or hyperpigmented. They may be of any shape with well defined regular or irregular borders. Examples include cafe-au- lait spots, vitiligo, mongolian blue spot and port wine stain etc.

Papules. They are circumscribed raised skin lesions of less than 0.5 cm in diameter. Examples include molluscum contagiosum, warts and miliaria rubra (prickly heat).

Nodules. Nodules are elevated skin lesions larger than 0.5 cm in diameter. They may be located in the epidermis, dermis or subcutaneous tissue. Examples include epidermoid cysts, fibromas, neurofibromas.

Tumors. Tumors are large nodules, generally > 2 cm in diameter. They may be benign or malignant and primary or metastatic.

Plaques. They arc well-circumscribed, broad-based lesions often formed by coalescence of a number of papules. The diameter or size of the lesions is greater than its height or elevation. A typical example is psoriasis.

Wheals. They are transient, raised edematous skin lesions with irregular edges. The lesions are erythematous with a central pallor. Intense itching is usually present. They can be seen in dermatographism (Darier’s sign and tachy cerebrale), urticaria, and insect bites.

Vesicles. The elevated, fluid-containing skin lesions of < 1.0 cm diameter are called vesicles. Examples include chicken pox, herpes simplex or zoster, and contact dermatitis.

Bullae. When vesicles are larger than 1.0 cm diameter, they are called bullae. They may be intraepidermal or subepidermal. Examples include epidermolysis bullosa and staphylococcal scalded skin syndrome.

Cysts. The circumscribed tumors Containing semisolid or fluid contents are called cysts. The typical example is epidermal cysts that occur after puberty on the face and upper back.

Pustules. The elevated well circumscribed skin lesions containing purulent material or pus are called pustules. Unlike the transparent dew drop appearance of vesicles, the pustules may be turbid or opaque and white or yellow in color. Examples include folliculitis or pyoderma.

Comedones. These are characteristic skin lesions of acne distributed on the face and upper back. Open comedones or black heads are 2-5 mm flesh colored papules with black centers. The closed comedones or white heads are 1-3 mm flesh colored papules with a pin point opening.

Purpura. The leakage of blood in the skin is called purpura. Unlike erythematous macules, purpura cannot be blanched by pressure with a finger or preferably with a glass slide or a transparent plastic spatula (diascopy). Petechiac are small, pinpoint areas of hemorrhages while ecchymoses are large areas of extravasation of blood in the skin. Ecchymotic skin patches may be flat or raised above the surface when there is associated vasculitis viz. Henoch- Schonlein purpura and collagen vascular disorders .

Burrows. They are linear skin lesions produced by the adult female mite as she tunnels into the stratum corncum. There is a black dot at the leading edge of the tunnel due to the lodgement of mite. Burrows are typically located in the interdigital areas of palms and soles.

The primary lesions enable classification into broad groups of skin disorders which is useful for considerations of differential diagnosis. The broad groups of primary skin lesions include maculo-papular, papulo-squamous, vesiculo-bullous, tumor-nodules, vascular reactions (urticaria, purpura), eczematous and pigmentary changes.

Secondary Lesions

They are produced due to changes affected by scratching, touching, secondary infection and due to local and systemic effects of medications.

Crusts. They are formed by drying of blood, serum and any exudate overlying the diseased skin. They are often present in impetigo, in which they appear honey-colored and in infants with weeping eczematous lesions.

Excoriations. They develop as a result of linear losses of skin secondary to self-induced scratching and rubbing. Common examples include contact dermatitis, atopic dermatitis and insect bites.

Ulcers. They occur due to deeper loss of the skin involving both epidermis and a variable depth of dermis or subcutaneous tissue. They may result from infection, vascular insufficiency or burns.

Fissures. They are linear clefts deep through the epidermal layer in thickened or chronically inflamed skin.
Lichenification. The exaggeration of skin markings due to chronic rubbing due to allergic or infective skin lesions is called lichenification.

Atrophy. Atrophy of skin refers to loss or thinning of the epidermis or dermis. Epidermal atrophy is characterized by wrinkling of skin with telangiectases. In dermal or subcutaneous atrophy, the skin is depressed.

Eczematous skin lesions. It refers to inflammatory skin lesions which have indistinct margins with erythema and vesiculation in the acute phase. Scaling, crusting and lichenification may be seen as the disorder progresses.
Hyperkeratosis. It is a histologic term used to describe thickening of the stratum comeum. The presence of thick rough scales over skin lesions is a good clinical marker of hyperkeratosis.

Shape of Skin Lesions

The con figuration of skin lesions may provide useful diagnostic clues. Linear lesions occur in a line and are characteristically seen in contact dermatitis and incontinentia pigmenti. Tachycerebrale is an erythematous raised linear streak that appears within 30 to 60 secnds after scratching with a fingernail or a sharp object. It may be elicited in patients with encephalitis, meningitis and other acute CNS inflammatory diseases. Annular or ring shaped lesions are seen in children with ring worm (tinea corporis), pityriasis rosea and nummular eczema. Semicircular or arc-like (arciform) lesions are suggestive of erythema marginatum. The grouped lesions are called as herpetiform lesions and are seen in herpetic infections. Reticulated eruptions give a netlike or interlacing pattern as seen in patients with erythema infectiosum and incontinentia pigmenti. A number of other descriptive terms are used that often connote a specific disease entity. For example, discoid (disk shaped) usually refers to discoid lupus erythematosis, nummular (coin shaped) to a type of eczema and guttate (droplike) to a form of psoriasis.

Distribution of Rash

The distribution of skin lesions should be carefully examined and may provide useful diagnostic clues. In scabies face is characteristically spared (except in infants) and lesions are mostly concentrated over the interdigital areas of palms and soles and genital region. The presence of rash on the face may provide diagnostic clue to the underlying collagen vascular disorder. Systemic lupus erythematosus is characterized by a typical sunlight-sensitive butterfly rash over the cheeks with marked erythema and papulo-vesicular lesions. Heliotropic or lilac discoloration of the eye lids with periorbital edema is highly suggestive of dermatomyositis. In addition, there is scaly erythematous dermatitis over the bony prominences such as metacarpophalangeal, proximal interphalangeal joints, knees, elbows and medial malleoli. Erythema of palms and soles with or without desquamation is a recongnized feature of prolonged steroid therapy, hepato-cellular failure, scarlet fever, hand foot and mouth disease, Kawasaki disease, and rocky mountain spotted fever. Skin rash over the exposed parts of the body (face, extremities, hands and feet) due to photo-sensitivity is a characteristic feature of a number of disorders.

Causes of photo-sensitivity skin rash
  • Pellagra
  • Hartnup disease
  • Porphyria erythropoeitica
  • Drugs (Phenothiazines, non-steroidal anti-inflammatory drugs, topical agents, Cosmetics etc.)
  • Phytophotodermatitis (Psoralen containing fruits and plants)
  • Xeroderma pigmentosa
  • Cockayne syndrome
  • Bloom syndrome
  • Rothmund – Thomson Syndrome

Color of Skin Lesions

Macular erythematous skin lesions are most common. They occur due to viral exanthems as a result of dilatation of superficial cutaneous blood vessels. Erythema readily blanches on pressure. Purpuric skin lesions do not blanch on pressure and they undergo color changes from bright pink to bluish pink, blue and dark brown over several days. Petechiae and ecchymoses may occur due to thrombocytopenia, vasculitis and life-threatening viral, bacterial and treponemal infections. The skin lesions may become lighter in color (hypopigmentalion) after healing and recovery. Depigmentation refers to total loss of pigment secondary to an autoimmune disorder (vitiligo) or due to hereditary disorders like partial and complete albinism. The cafe-au-Iait spots should be differentiated from ncvocellular nevus by irregular border and lighter color. Carotenemia produces yellowish discoloration of skin akin to jaundice but there is no discoloration of sclera.

Appendages of Skin

Hair and nails provide protection to the skin and have common embryologic origin or background. Many developmental or acquired skin disorders may have associated abnormalities in the hair, nails, and teeth. Several acquired disorders of skin are associated with abnormalities in the mucous membranes, hair and nails. Ectodermal dysplasia is characterized by hyperthermia (fever due to rise of environmental temperature because of absence of sweat glands), alopecia, absence of eyebrows and eyelashes. Hypertrichosis or excessive generalized growth of body hair over the non-sexual areas of the body is seen in a number of systemic disorders.

Systemic conditions asociated with hypertrichosis
  •  Familial or constitutional
  •  Drugs like corticosteroids and phenytoin
  •  Cushing’s syndrome
  •  Chronic malnutrition or starvation
  •  Porphyria cutanea tarda
  •  Coffin-Siris syndrome
  •  Cornelia de Lange syndrome
  •  Treacher-Collins syndrome (Hair on the side of face)

Scalp should be examined for seborrhea, discoid lesions of tinea capitis and psoriasis, alopecia, pediculosis and depigmentation. Rarely, hair may show alternate bands of depigmentation producing typical flag sign in children with kwashiorkor. A number of systemic disorders are associated with sparse light-brown and brittle scalp hair. Many of these disorders are associated with a variety of skin manifestations.

Causes of sparse, light-brown and brittle/abnormal scalp hair
• Kwashiorkor                                                • Congenital syphilis
• Cretinism                                                     • Idiopathic yperparathyroidism
• Chronic debilitating disease                    • Zinc deficiency
• Progeria                                                       • Copper deficiency
• Ectodermal dysplasia                                • Acrodermatitis enteropathica
• Hypervitaminosis A                                  • Biotinidase deficiency
• Acrodynia                                                    • Anorexia nervosa
• Adrenal insufficiency                                • Homocystinuria
• Cartilage-hair hypoplasia syndrome     • Mcnke’s syndrome (Kinky hair disease)
• Langer-Giedion syndrome                       • Alopecia areata
• Hallermann-Streiff syndrome                 • Traction alopecia (“pony-tail alopecia)
• Trichotillomania                                        • Tinea capitis
• Trichorrhexis nodosa                                • Coffin – Siris syndrome
• Incontinentia pigmenti                             • Polyendoeririe deficiency
• Conradi disease                                          • Drug induced

Pitting of nails along with thickening, loss of lustre and subungual keratosis may occur in psoriasis, atopic dermatitis and onychomycosis. White spots or vertical lines in the nails (leukonychia) may be caused by trauma, nutritional deficiency and chronic debilitating disorders. Dystrophic nails is a recognized feature of epidermolysis bullosa, ectodermal dysplasia, chondro-ectodermal dysplasia and nail patella syndrome. Dysplasia of nails is seen in infants with fetal alcohol and phenytoin syndromes. Tuberous sclerosis may have associated subungual and periungual fibromas arising from the groove of the nail beds of fingers and toes.

Some Common and Unusual Skin Conditions

There are a number of relatively common and some’unusual skin conditions which should be correctly identified by the pediatrician. The salient diagnostic clinical features are given below. The list is merely representative and in no way exhaustive.

Scabies. The characteristic lesions are linear burrows with black dots at the leading edge mostly over the axillae, beltline, flexor surfaces of extremities especially wrists, interdigital areas of palms and soles and genital region. The face is usually spared except in infants. There is intense and intractable itching especially at night. There is secondary excoriations, eczematous areas, pustules and crusting due to itching, rubbing and secondary infection. The disease is highly contagious and several family members are affected simultaneously.

Atopic dermatitis. The distribution of skin rash in atopic dermatitis varies depending upon the age. In infancy cheeks, wrists and extensor surfaces of the arms and legs typically develop papulo-vesicular, often weeping or wet lesions, which may develop fine scabs or lichenification. The scalp and postauricular areas are often affected while diaper area is usually spared. Secondary infection and traumatic lesions may develop due to scratching and rubbing. In older children, dry maculopapular lesions are mostly distributed over the flexor surfaces of extremities, neck, wrists and ankles. Xerosis and lichenfication commonly supervenes. Eosinophilia and elevation of serum IgE levels provide useful laboratory support to the diagnosis.

Seborrheic dermatitis. Seborrheic dermatitis is usually associated with seborrhea (dandruff) and has predilection for infants and adolescents. The condition starts from scalp with greasy-yellowish scalcs and extend down the forehead to involve the eyebrows, nose and ears. Intertriginous areas and diaper area may be affected due to supcradded Candida infection. Loss of scalp hair and depigmented skin lesions are seen during the course of the disease. The clinical differentiation from atopic dermatitis may be difficult at times. Absence of eosinophilia and normal serum lgE levels support the diagnosis of seborrheic dermatitis.

Papular urticaria. It is a common, intensely pruritic disorder caused by an allergic response to insect bites. The fresh lesions are papules with a punctum on an erythematous base on the exposed skin surface. Most cases occur during summer and spring due to mosquito and flea bites. Excoriations and secondary infection may lead to hyperpigmentation in older lesions.

Nutritional disorders

Zinc deficiency. Skin manifestations are characteristically seen around the perioral, periorbital and perianal areas. Distal parts of limbs especially hands and feet also develop skin manifestations. The vesiculo-bullous skin lesions soon become dry, scaly and crusted lesions with sharply demarcated borders. The vesicles rapidly rupture, revealing a moist, red base and then dry and become plaquelike. Diarrhea and alopecia are commonly associated. Affected infants are irritable, listless and fail to thrive.

Essential fatty acid deficiency. It is characterized by generalized scaly dermatitis composed of thickened, erythematous, desquamating plaques. Alopecia, thrombocytopenia and failure to thrive are often associated.

Skin lesions with fine scales

Pityriasis alba. It is a common, asymptomatic skin condition of unknown etiology (may be due to S.albus) in infants and young children. The skin lesions are well demarcated hypopigmented round or oval patches with minimal fine scales. The lesions, 1-3 in number, most commonly occur on the face but may be present on the neck, upper trunk and proximal parts of limbs.

Pityriasis versicolor. It is characterized by appearance of asymptomatic ovoid or coin shaped brown colored or whitish macules over the neck, chest and back. The lesions have fine adherent scales. Pruritis is usually absent or minimal. Most cases occur after puberty though younger children may contract the infection from their infected mothers.

Pityriasis rosea. It is a common disorder usually seen in adolescent children and young adults. The rash may be preceded by mild constitutional symptoms such as fever, headache, malaise and arthralgia. In half the patients, there is an oval flesh colored herald patch on the trunk measuring 1-10 cm in size. After a few days of herald patch, generalized skin rash appears on the trunk. The eruption consists of oval flesh colored or pink macules with central clearing and raised fine scaly edges. The skin lesions are usually symmetric and their long axis follows lines of cleavage resulting in a pattern of Christmas tree on the back. Ttching is minimal or absent. The disorder is often mistaken with tinea corporis and skin lesions at times are described as “lots of ringworm” by the young resident. The eruption continues to evolve for about 2 weeks and skin lesions usually persist for 3-8 weeks and at times for several months.

Fungus infections of skin

Tinea capitis. There are no characteristic features. It often presents as a kerion with an inflammatory, boggy, pustular patch with localised alopecia of scalp. The typical scaly circular lesion with raised edges and central clearing that is seen in tinea corporis is uncommon in tinea capitis. There is eczematization, scab formation and development of scales. The condition should be diffemtiated from seborrheic dermatitis, pustular folliculitis and trichotillomania. The KOH preparation is not reliable in tinea capitis and diagnosis is best confirmed by fungal culture.

Tinea corporis. It is characterised by annular erythematous ring lesions with active elevated margins and central clearing. The border is generally scaly, slightly elevated and often studded with microvesicles and tiny pustules. The lesions may be single or multiple. Tinea corporis should be differentiated from herald patch of pityriasis rosea, granuloma annulare and dry nummular eczema.

Candida infection. Candida infection of skin has special predilection for moist areas like diaper area, neck, axillae and groin, prioral and perianal regions. It produces confluent erythema with maceration and fissuring. There are vesiculo-pustular lesions over an erythematous base. Oral thrush and paronychial candidal infection may coexist. Congenital cutaneous candidiasis is characterized at birth or within 12 hours of life by multiple erythematous macules or vesiculo-pustular lesions. After neonatal period, development of candidiasis should alert the pediatrician to look for an underlying cell-mediated immunodeficiency disorder, HIV infection, diabetes mellitus, hypoparathyroidism (Di George syndrome), Addison’s disease, biotinase deficiency, and malignancy.
Erythema multiforme. It is characterized by erythematous lesions of pleomorphic morphology. The lesions begin as erythematous macules and evolve into papules, vesicles, bullae, urticarial plaques or patches of confluent erythema. The pathognomonic lesions of erythema multiforme are iris or target shaped lesions which have a dusky center, an inner pale ring and an erythematous outer border. The symmetric crops of skin lesions usually occur on extensor surfaces of arms and legs often involving palms and soles. The skin lesions may heal over 4-6 weeks with hypopigmentation or hyperpigmentalion but without any scarring. When skin lesions arc associated with involvement of two mucous membranes, the condition is called as Stevens-Johnson syndrome.

Granuloma annulare. It is an uncommon chronic skin disorder affecting school children and young adults. It is characterized by appearancc of semilunar or arciform flesh colored or pink smooth papules. The lesions coalesce to assume oval, round or ringlike shape with central clearing. The size of lesions varies between 1-5 cm, single or multiple, may occur anywhere on the body but most commonly over the extremities. The skin lesions are smooth, without any scales or epidermal involvement. Skin lesions are asymptomatic and may take few months to 2 years to resolve spontaneously. Absence of epidermal involvement, lack of scales, multiple lesions without itching differentiate granuloma annulare from tinea corporis.

Graft-versus-host disease (GVHD). The acute form of GVHD manifests with maculo-papular rash (which may progress to toxic epidermal necrolysis in a fulminant case) with diarrhea, tachypnea andhepatosplenomegaly. The chronic form of GVHD is characterized by hyperkeratotic skin rash, hepatosplenomegaly, hair loss, chronic diarrhea and wasting.

Toxic epidermal necrolysis. It is characterized by loosening of large sheets of epidermis with formation of flaccid bullae. The bullae rupture leading to exposure of intensely pink, underlying epidermis or dermis which gives an appearance of scalded skin. Nikolsky sign is poisitive i.e. epidermis can be readily peeled by rubbing the skin at the normal sites. The condition may occur due to toxins of S. aureus or follow ingestion of certain drugs.

TORCH infections. Intrauterine infections may show manifestations of petcchiae and ecchymoses over trunk and extremities due to thrombocytopenia. “Blue berry muffin” spots arc discrete, well-circumscribed skin lesions due to dermal erythropoiesis in severely affected infants with congenital CMV infection

Congenital syphilis is characterized by raaculo-papular rash initially oval and pink but subsequently turn coppery brown with desquamation especially over the palms and soles. A characteristic vesiculobullous eruption with erythema, blister formation and crusting may occur over the extremities, palms and soles.