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PrinciplesofPediatricDermatology
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SKIN MANIFESTATIONS OF METABOLIC DISEASES
This chapter summarizes the different cutaneous manifestations of certain systemic
diseases.
The skin is a clear mirror of the human body where internal diseases may be reflected on
the skin surfaces.
There are different internal diseases that can cause skin manifestations . These signs may
appear on the skin surface with different clinical features depending mainly on the primary
internal disease:
Skin color
Different skin colors are associated with certain skin diseases.
Pallor : as in anemia .
Earthy yellowish discoloration of the skin: occurs in chronic intestinal infestations such as in
bilharziasis.
Plethoric: due to hyperkinetic circulation as in erythroderma and congestive heart failure.
Dryness of the skin occurs in chronic debilitating diseases .
Thinning of the skin: is due to exhaustion of dermal collagen such as in cachexia or locally
due to topical potent steroids.
Stria of the skin: occur in Cushings disease, after topical and systemic steroids for a long
period, dupuytrens contracture and in chronic liver diseases.
Shape: changes in the form and shape of the skin such as moon face due systemic steroids
and lymphangitis and gynecomastia that is related to increased circulating estrogens.
Hair changes: fine , lanugo hair covering the skin may become pigmented as in some
tumors mainly carcinomas .
Hirsutism: this is caused by increased circulating androgens and cortisol due to Cushings
disease or systemic steroid treatment and certain ovarian tumors .
Alopecia: may develop due to increased circulating androgens or changes in the sensitivity
of androgen and estrogens receptors in the skin.
Changes in the color of hair: metabolic and deficiency diseases such as Kwashiorkor and
porphyries may cause change in the color of hair.
Falling of hair: in anemia, hormonal disorders, after chemotherapy or psychic trauma .
Nail changes: this occurs in chronic diseases such as pernicious anemia, liver cirrhosis
leading to white bands and clubbing of nails.
Xanthomatosis, acne and seborrheic like dermatitis occurs in hepatobiliary diseases.
Pruritus is a common manifestation of liver diseases that is believed to be related to bile
salt stasis and increase in its concentration in the blood. Cholestyramine increases fecal loss
of bile salts and thus relieves itching.
Edema of skin may be due to hypoalbuminaemia, increased venous pressure and increases
capillary permeability.
Erythroderma: erythema and exfoliation of skin may result from drug eruption and
Papulosquamus diseases such as psoriasis.
Urticarial lesions and alopecia areata: is related to deep psychic trauma.
2.
3.
Spider naevi, telengectasia, palmer flush, livedo reticularis and vasculitis are
common manifestations in children.
4.
5.
6.
Seborrhea and acniform eruption on the upper part of the body is common
manifestations.
7.
8.
Biers spots: white areas appear on the lower extremities when cooled .
9.
Nails: changes in nails with absent lanula and nail clubbing in liver cirrhosis.
CUSHINGS DISEASE
The different skin manifestations are:
1.
2.
Acne: due to excessive androgen secretion forming keratotic plugs occluding the pilo
sebaceous gland orifices is a common manifestation of Cushings syndrome. The
lesions are in the form of superficial papules and pustules with minimal black heads.
This type covers different areas of the skin surface and unlike acne vulgaris, which
affects seborrheic areas of the face, back, and upper chest.
3.
1.
Striae: this is due to the increased circulating glucocorticosteroids. Skin lesions are
pinkish in color arranged usually in linear shapes .Old striae due to Cushings disease
retains its blue- pink color in contrast to the other types of striae which become faint
whitish streaks later on.
2.
3.
4.
Superficial fungal infections : Tinea versicolor is also one of the manifestations seen
in Cushings syndrome.
Pruritus .
Hyperpigmentation or vitilligo .
Premature hair graying .
Alopecia and hair loss on the eye browse .
The nails :become brittled and disfigured .
Diffuse hyperpigmentation : of the buccal mucosa and skin usually on the sun
exposed areas of the face, neck and extremities , due to increased production of
melanin. Skin creases of the palms ,sites of friction , old scars and previous
pigmented areas become darker.
2.
3.
2.
Fig.352 Necrobiosis
lipodeca diabeticorum
1.
Granuloma annulare: The lesions are pale or flesh colored papules forming rings
which blanche with pressure, showing characteristic beaded ring of dermal white
papules mainly on the back of the fingers and hands . Granuloma annulare can be
caused also by tick bites and drug eruption .
2.
3.
Diabetic dermopathy : The skin lesion is in the form of dull red , oval papules and
may show small blisters, which ulcerate leaving small erosions healing with atrophic,
pigmented patches.
Drug reactions: this is due to the oral medications as sulphonylureas leading to erythema
multiforme and phototoxic reactions.
Xanthomatosis: The lesions appear in later stages of diabetics due to increased serum
lipids .
Trophic ulcers and bullous lesions : due to diabetic neuropathy mainly on the feet .
Skin manifestations:
Dry scaly skin .
Dermatitis herpetiformis .
Fine hair .
Skin pigmentation of the mucous membrane of the buccal cavity and skin creases
are increased in some cases of intestinal malabsorption.
2.
3.
Acrodermatitis enteropathica.
This is a genetic disorder that may be due to zinc deficiency as in malabsorption
syndrome. The condition may be fatal in infants and young children.
Clinical Features.
Skin lesions.
Candidiasis like lesions appear on peri-oral, around the genitalia, scalp, elbows and
fingers. The skin eruption is small blisters, pustules, erosions, crusting and scaling
lesions.
Hair and nail loss
General manifestations
Acrodermatitis enteropathica may be accompanied by severe diarrhea leading to
cachexia.
Diagnosis depends on the clinical picture and the decrease in the circulating zinc.
4.
Vasculitis
Intestinal malabsorption may be associated with skin and bowel vasculitis.
5.
Dermatitis herpetiformis
Dermatitis herpetiformis is an immunologic problem due to deposition of IgA at the
dermo epidermal junction .The condition affects all age groups but mainly in middle
aged females.
The skin lesion begins as a small severely pruritic papules on an erythematous base
on the extensor surfaces of the limbs and trunk. Dermatitis herpetiformis is usually
accompanied by coeliac disease.
Eczema, scabies, erythema multiformis simulate dermatitis herpetiformis and some
times it is not easy to differentiate skin lesions.
The condition responds well to Dapsone and Sulphapyridine.
REFERENCES
1.
Callen JP, Jorrizo JL, eds. Dermatological Signs of Internal Disease. Philadelphia:
Saunders, 1988.
2.
Jones JH, Mason DK, eds. Oral Manifestations of Systemic Disease. Philadelphia:
Saunders, 1980.
3.
Braverman IM. Skin Signs of Systemic Disease 2nd edn. Philadelphia: Saunders,
1981.
4.
Lang PG. Pituitary disorders. In: Callen JP, ed. Cutaneous Aspects of Internal
Disease. London: Year Book Medical Publishers, 1981: chapter 39, 463-71.
5.
Barth JH, Ng LL, Wojanarowska F et al. Acanthosis nigricans, insulin resistance and
cutaneous virilism. Br J Dermatol 1988; 118: 613-19.
6.
Callen JP. Skin signs of internal malignancy. Austral J Dermatol 1987; 28: 106-14.
7.
8.
9.
10.
Brown J, Winkelmann RK, Randall RV. Acanthosis nigricans and pituitary tumours.
Report of eight cases. J Am Med Assoc 1966; 198: 619-23.
11.
PORPHYRIN DISORDERS
Porphyrins are metabolic by-products, that have not followed the usual synthesis from
glycine and succinyl co-enzyme A to heme with production of Porphobilinogen and
aminolevulinic acid. Different factors such as drugs , chemicals and hormones can increase
porphyrin synthesis.
The site of disturbance is either in the liver (hepatic porphyria) or in the bone marrow in the
erythroid cells (erythropietic porphyria ).
Types of porphyria
A
Associated diseases
Liver cirrhosis, hemochromatosis, carcinomas and Hodgkins disease may be associated with
porphyria cutanea tarda.
Diagnosis
Urine shows a pinkish coral red fluorescence under Woods light .
Positive bromosulphalin test.
Detection of Porphyrins in urine and feces .
Three-step procedure (devised by Castro): Disposable plastic column charged with anion
exchange resin, permits detection of various porphyrins as well as their precursors.
Hereditary Porphyria Cutanea Tarda
This is a rare type, which is carried as a dominant gene and appears at early age around 15
years of age.
Treatment
Phlebotomy: 500ml of blood every two weeks. Usually 3000-5000 ml of blood is taken .
Involution of skin lesions usually appear after the second blood intake .
Chloroquine: 500mg twice weekly for the adult age are believed to have an encouraging
results.
Sodium bicarbonate: used to alkalinize urine may have a beneficial effect.
Skin manifestations:
Skin pigmentation.
Hirsutism.
Photosensitivity is not a feature of this type .
PORPHYRIA VARIAGATE
Skin manifestations include those of porphyria cutanea tarda and acute intermittent
porphyria but occurring in earlier age groups.
ERYTHROPOIETIC PORPHYRIA
Photosensitivity causes polymorphous light eruption leading to pruritic, erythematous
papulo vesicular and urticarial rashes mainly on the sun-exposed areas. Skin lesions heal
leaving linear pitted scars .Other manifestations are purpura , oedema and severe burning
pain.
ERYTHROPOIETIC PROTOPORPHYRIA
This type appears early in childhood from 2-5 years of age and inherited as a dominant
trait. Photosensitization is a characteristic feature of erythropoietic protoporphyria . In this
type it is believed to be due to the longer wavelengths of ultraviolet (UVL) which ranges
from 320-450nm. Ordinary window glass offers no protection from the effect of sun on such
patients.
Clinical Manifestations
Skin lesions are pruritic erythematous, plaque-like edema, wheals and even vesicles or
bullae on the sun exposed areas. The skin lesions may heal with scarring with waxy
thickening of the nose, cheeks, over the proximal finger joints, circumoral atrophy and
scarring.
Diagnosis
Characteristic cutaneous lesions.
Photosensitivity.
Increased proto-and coproporphyrins in feces.
PHENYLKETONURIA
This disease affects children with blond hair, blue eyes and fair skin due to lack of the
enzyme phenylalanine hydroxylase, which is essential for degradation of phenylalanine to
tyrosine.
Clinical Features:
Photosensitivity.
Eczema like reaction.
Secondary infections are common.
Scleroderma-like skin lesions.
Induration of thighs and buttocks are common manifestations in affected infants and
children.
General manifestations.
Mental deficiency.
Epileptic seizers.
Laboratory findings.
Presence of phenyl pyruvic acid in urine. This can be easily detected by adding to urine few
drops of ferric chloride solution that will give deep green color.
Treatment
Special diet for infants and young children containing low phenylalanine and this should be
given immediately after birth.
Fig.354. Xanthomatoses
Fig.355. Xanthomatoses
Fig.355d. Xanthomatosis
Xanthomatosis
Fig.355e.
Tendinous xanthomas: nodular yellowish lesions appear on the tendons on the extensor
surface due to cholesterol infiltration.
Tuberous xanthomas: symmetrical nodular lesions, appear over the extensor surface of
the joints and accompanied by increased serum triglycerides and cholesterol.
MANIFESTATIONS OF HYPERLIPOPROTEINEMIA
1
Primary Hyperlipoproteinemia
Familial hyperlipoproteinemioa
Different types:
Type I hyperlipoproteinemia
Type II hyperlipoproteinemia
Type III hyperlipoproteinemia
Type IV hyperlipoproteinemia
Type V hyperlipoproteinemia
2
Secondary Hyperlipoproteinemia
Secondary to systemic diseases
Xanthomatous biliary cirrhosis
Hematopoeitic diseases
Xanthoma diabeticorum
Lipoid nephrosis
Myxedema
Pancreatitis
Generalized xanthelasma
Histiocyhtosis X
Litterer -Siwe disease
Hand -Schuller-Christian disease.
Eosinophilic granuloma.
Juvenile xanthogranuloma.
Refsums Syndrome
This syndrome is a genetic disorder of lipid metabolism.
Neurological and cutaneous features characterize this syndrome.
The underlying abnormality is a deficiency in phytanic acid, displacing unsaturated fatty
acids as linolenic acid from tissue lipids.
Clinical Manifestations
Skin manifestations are mainly dryness of the skin, which simulate icthyosis vulgaris.
General manifestations begin early in childhood similar to retinitis pigmentosa with
different neurological (polyneuropathy), ataxia, cardiac and bone manifestations.
ALKAPTINURIA
This syndrome is due to deficiency in homogentisic acid oxidase leading to accumulation of
homogentisic acid that can be detected in urine.
Clinical Features
In early life: dark urine and sweat.
Arthropathy of spines and knees due to chondreal cartilage thickening.
In older age groups the skin of forehead, ears, cheeks and around the eyes is pigmented.
Pigmentation of the sclera.
HOMOCYSTINURIA
This disease is due to disorder in methionin metabolism due to an absence of hepatic
cystathione synthetase causing abnormality in collagen formation.
Clinical Features
The clinical manifestations appear early, in the first year of life.
Thin, yellowish skin and atrophic scars.
Fine sparse hair, which brittles easily due to disulfide bond reduction.
Intravascular clotting leading to livedo reticularis.
Treatment
Diet low in methionin.
Supplement by pyridoxine and cysteine may give good improvement.
HARTNUP DISEASE
This error of metabolism of tryptophane leads to nicotinic acid deficiency.
The changes occur early in infancy due to unabsorbed tryptophene, which is broken into the
gut to indoles that is absorbed, metabolized and excreted in urine as indican.
Clinical Features
Skin manifestations are like pellagra in the form of dry, scaly and sharply demarcated rash
on the sun-exposed areas.
Photosensitivity.
Neurological manifestations: ataxia and mental retardation.
Diagnosis
By the clinical picture.
Pellagra like eruption.
Neurological manifestations, ataxia and mental disturbances.
Urine examination shows increase in indican and monocarboxylic amino acid.
Treatment
Nicotinamide.
Treatment of skin manifestations by emollients and keratolytics as topical salicylic acid in an
ointment base alone or in combination with steroids (Locasalene).
Sunscreens and avoiding too much exposure to sunlight.
LITTERER-SIWE DISEASE
This disease appears early in infancy in the first months of life.
Clinical Features
Skin manifestations
The skin manifestations are brown, scaly papules on the seborrheic areas on the scalp,
behind the ears, naso-labial folds and mid chest.
Systemic manifestations include purpura, systemic histiocytosis and malignancy.
Most infants die in the first two years from infections mainly due to pneumonia.
Treatment
Treatment is not always curative.
Antibiotics for pulmonary infections.
Corticosteroids.
Cytosine and blood transfusion can be tried.
REFERENCES
1
Kappas A, Sassa S, Galbraith RA et al. The porphyrias. In: Scriver CR, Beaudet AL,
Sly WS et al., eds. The Metabolic Basis of Inherited Disease 6th edn. New York:
McGraw-Hill, 1989: 1305-65.
Moore MR, McColl KEL, Rimington C et al. Disorders of Porphyrin Metabolism. New
York: Plenum Medical, 1987: 15.
The Metabolic Basis of Inherited Disease 6th edn. New York: McGraw-Hill, 1989:
1645-54.
Barranger JA, Ginns EI. Glucogyl ceramide lipidoses: Gauchers disease. In: Scriver
CR et al., eds. The Metabolic Basis of Inherited Disease 6th edn. New York: McGrawHill, 1989: 1677-98.
10
Brady RO, King FM. In: Hers HG, van Hoof F, eds. Lysosomes and Storage Disease.
New York: Academic Press, 1973: 439.
11
Forsythe WI, McKeown EF, Neill DW. Three cases of Niemann-Pick disease in children.
Arch Dis Child 1959; 34: 406-9.
12
13
Rosenberg LE, Scriver CR. Disorderes of amino acid metabolism. In: Bondy PK,
Rosenberg LE, eds. Metabolic Control and Disease. Philadelphia: WB Saunders, 1980:
709.
14
15
16
Goldstein JL, Brown MS. In: Scriver CR et al., eds. Metabolic Basis of Inherited
Disease 6th edn. New York: McGraw-Hill, 1989: 1215-50.
17
18
Pucevich MV, Lataur DL, Bale G et al. Self-healing juvenile cutaneous mucinosis. J Am
Acad Dermatol 1984; 11: 327-32.
19
20
Pucevich MV, Latour DL, Bale GF et al. Self-healing juvenile cutaneous mucinosis. J
Am Acad Dermatol 1984; 11: 327-32.
21
Gebhart W. Heritable metabolic storage diseases. J Cutan Pathol 1985; 12: 348-57.
22
Scriver CR, Mahon B, Levy HL et al. The Hartnup phenotype: mendelian transport
disorder, multifactorial disease. Am J Hum Genet 1987; 40: 401.
23
Wells GC. Skin disorders in relation to malabsorption. Br Med J 1962; ii: 937.
24
Miller S. Nutritional deficiency and the skin. J Am Acad Dermatol 1989; 21: 1-