DR. MAHMOUD HIJAZY 

Principles of Pediatric Dermatology

http://www.drmhijazy.com/english/chapters/chapter42.htm

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 Cushing‘s disease, after topical and systemic steroids for a long period, dupuytren‘s 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 Cushing‘s 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.

 

SKIN MANIFESTATIONS OF LIVER DISEASES

The pathological changes in the skin and its appendages in liver disease are:

1. Jaundice in chronic liver diseases .2. Diffuse hyperpigmentation of the skin due to hepato-cellular damage.3. Spider naevi, telengectasia, palmer flush, livedo reticularis and vasculitis are

common manifestations in children.4. Purpuric rashes are due to vitamin K deficiency.5. Hair :is fine in liver diseases.6. Seborrhea and acniform eruption on the upper part of the body is common

manifestations.7. Decreased  testicular androgens due to hepatic dysfunction leads to fine hair in

adults and gynecomastia.8. Bier‘s spots: white areas appear on the lower extremities when cooled .9. Nails: changes in nails with absent lanula and nail clubbing in liver cirrhosis.

 

SKIN MANIFESTATIONS OF RENAL DISEASES

Pruritus: is a common manifestation of renal failure . The exact mechanism is not clear and may be related to secondary hyperparathyroidism that leads to mast cells proliferation.

Dryness of the skin: dryness of skin in renal disease may be related to different factors mainly:

Excretion of nitrogen containing compounds on to the skin surface. Decreased sebaceous gland activity leads to more dryness and also increases the viscous cycle of itching .

Impaired androgen metabolism: increases dryness of the skin. This also causes fine scalp hair, with falling of axillary and pubic hair after puberty.

Skin color changes: This is due to increase of melanocyte stimulating hormone occurring in chronic renal failure  since the kidney is the major site of metabolism of this hormone . The skin color in renal failure varies from pallor due to anemia and hyperpigmentation due to increased melanocyte activity .

 

SKIN MANIFESTATIONS OF ENDOCRINE DYSFUNCTIONSPITUITARY DISEASES

Different skin manifestations are related to pituitary dysfunction :

Acromegaly : The skin is thick due to increased collagen related to increase in circulating growth hormone leading to coarse features and tendency of keloids formation, skin tags and folds on the scalp (cutis verticis gyrata ).

The skin in acromegalic patient is greasy and pigmented and covered by thick coarse dark hair.

Hypopituitrism: The skin is dry, thin, atrophic leading to wrinkles, which are apparent mainly on the face with hypopigmented, faint yellowish brown patches.

 

CUSHING‘S DISEASE

The different skin manifestations are:

1. Hyperpigmentation :which is due to increase in the melanocyte-stimulating hormone (MSH).

2. Acne: due to excessive androgen secretion forming keratotic plugs occluding the pilo sebaceous gland orifices is a common manifestation of Cushing‘s 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. Hirsutism : This is due to increased circulating androgen that is related to increased androgen production .

 

Fig .350 Cushing's disease Fig 351. Cushing's disease

 

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 Cushing‘s disease retains its blue- pink color in contrast to the other types of striae which become faint whitish streaks later on.

2. Purpura : is a common manifestation . Atrophy of dermal collagen leads to less support of the dermal vessels , which become liable to rupture .The presence of purpura in children and young ages should raise the possibility of Cushing‘s syndrome .

3. Moon face : this may be due to hydration of subcutaneous fat .4. Superficial fungal infections : Tinea versicolor is also one of the manifestations seen

in Cushing‘s syndrome.

  

SKIN MANIFESTATIONS OF THYROID DYSFUNCTION

Skin manifestations of Hyperthyroidism

Pretibial myxedema: is the most characteristic features of thyrotoxicosis appearing as shiny waxy papules and plaques having orange-skin appearance on the chin of the tibia.

Increased hair of the areas involved.

Eczema : the lesions simulate atopic dermatitis in children and adults.

Skin thickness: is increased leading to coarse folds which is apparent more around the eyes. The skin in myxedema appears as a coarse, dry, scaly, puffy and pale with coarse hair possibly due to increased circulating TSH.

Warm skin and increased sweating due to increased basal metabolic rate.

Pruritus .

Hyperpigmentation or vitilligo .

Premature hair graying .

Alopecia and hair loss on the eye browse .

The nails :become brittled and disfigured .

 

SKIN MANIFESTATIONS OF PARATHYROID DYSFUNCTION

Hyper parathyroidism: may cause pruritus, cutaneous calcification, hemorrhage and infarction.

Hypoparathyroidism: cutaneous lesions may simulate that of muco-cutanous candidiasis.

 

SKIN MANIFESTATIONS DUE TO ADRENAL DYSFUNCTIONAddison‘s disease:

Skin manifestations of Addison‘s disease are due to increased melanin and androgen .These may cause different skin manifestations mainly:

1. 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. Virilism : due to increased circulating androgens leading to hirsutism , male pattern baldness.

3. Increased thickening of the skin : this is due to increased dermal collagen.

Acniform eruption and increased seborrhea of the skin and scalp due to increased androgens .

 

SKIN MANIFESTATIONS DUE TO PANCREATIC DISEASES

1. Necrobiosis lipoideca diabeticorum:

Skin lesions are granulomatous, firm, sharply demarcated, oval plaques of different sizes with shiny atrophic surface and characteristically yellow center. The lesions appear on the skin of diabetics mainly on the shins of the tibia due to collagen degeneration . The course is very chronic and healing is with scarring.

2. Bacterial and fungal skin infections mainly candidiasis.

 

SKIN MANIFESTATIONS OF DIABETES

Skin manifestations of diabetes include the following:

1. Necrobiosis lipodeca diabeticorum.

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. Vitilligo : there is an increased incidence of depigmentation of the skin in diabetics, which is lasting for a long period.

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.

5. Diabetic skin gangrene

Fig.353 Diabetic skin gangrene

Anhidrosis: is patchy due to diabetic neuropathy leading to heat intolerance.

Manifestations due to diabetes therapy

Lipodystrophy: at the sites of insulin injections .

Urticarial reactions due to insulin .

Drug reactions: this is due to the oral medications as sulphonylureas leading to erythema multiforme and phototoxic reactions.

 

Fig. 353b. Drug reaction due to diabetic therapy(Sulphonylurea)

Fig. 353b. Drug reaction due to diabetic therapy(Sulphonylurea)

 

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 OF INTESTINALMALABSORPTION SYNDROME

The clinical features are due to malabsorption of the essential fatty acids. These manifestations are more common in adults than in children.

1. 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. Other rare manifestations:

Bowel lymphoma and skin blistering due to epidermal necrosis in patients with carcinoma of the pancreas.

In children, the same manifestations may appear in those fed on linoleic acid deficient diet . The common skin manifestations are:

Psoriasiform rash.

Dryness , cracking and fissuring of the skin.

These cases improve with topical application of sunflower seed oil.

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. Kurwa A, Waddington E. Hepato-cutaneous syndrome (juvenile cirrhosis, allergic

capillaritis of the skin, proctocolitis and arthritis). Br J Dermatol 1968; 80: 839-40.8. McElgunn PS. Dermatologic manifestations of hepatitis B virus infection. J Am Acad

Dermatol 1983; 8: 539-48.

9. Isaacs NJ, Ertel NH. Urticaria and pruritus: uncommon manifestations of hyperthyroidism. J Allergy Clin Immunol 1971;48: 73-81.

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. Editorial. Pituitary-dependent Cushing‘s disease. Br Med J 1977; i: 1049-50. 

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. Hepatic porphyria, this includes:

Porphyria cutanea tarda

Acute intermittent porphyria

Porphyria variegata

B. Porphyria due to bone marrow disturbance :

Erythropoietic protoporphyria

Congenital erythropoietic porphyria (Gunther‘s disease )

 

PORPHYRIA CUTANEA TARDA

The clinical manifestations are due to abnormal Porphyrins metabolism. Drugs such as barbiturates, sulfonamides, chloramphenicol, chloroquine, griseofulvin and toxins, fungicides (hexachlorobenzene), may cause this type.

Different types of porphyria can cause different skin , hair and nail manifestations:

Clinical Manifestations

Skin manifestations

The skin is fragile, tear easily and forming blisters due to dermo epidermal separation.

Poikeloderma like reaction in the form of pigmentation , atrophy and telengectasia on sun exposed areas.

Hypopigmentation and scarring after healing.

Hypertrichosis is not a common manifestation of porphyria cutanea tarda.

Photosensitivity

The patients are sensitive to sunlight even when they are indoors. Patients are labile to have phototoxic reactions.

Associated diseases

Liver cirrhosis, hemochromatosis, carcinomas and Hodgkin‘s disease may be associated with porphyria cutanea tarda.

Diagnosis

Urine shows a pinkish coral red fluorescence under Wood‘s 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.

 

ACUTE INTERMITTENT PORPHYRIA(Porphyria hepatica)

This type is characterized by periodic attacks of abdominal colic, gastrointestinal disturbances, paralysis and psychiatric disturbances.

Clinical Manifestations:

General manifestations:

Abdominal colic.

Peripheral neuropathy.

Psychiatric abnormality.

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.

Increased porphyrins in red blood cells .

Fluorescent microscopic examination of blood : Few drops of blood are diluted 1:5 with normal saline are placed on a microscopic slide and examined by the oil immersion objective of a fluorescent microscope.

Erythrocytes usually show characteristic fluorescence.

It should be noted that in this type of porphyria , urine usually does not give fluorescence under the Wood‘s light .

 

CONGENITAL ERYTHROPOIETIC PORPHYRIA

This type is a hereditary disease, transmitted by an autosomal recessive gene. 

Clinical Manifestations

Skin manifestations

Skin manifestations appear early in infancy on the sun-exposed areas that are due to photosensitivity. Painful bullous lesions, which heal by destructive and disfiguring scarring and causing destruction of the cartilage of the nose, ears, and nails.

Cicatricial alopecia

Hypertrichosis: with hair on the cheeks, profuse eyebrows, and long eyelashes (“monkey face“).

Urine shows high amount of copro and uropophyrines.

Diagnosis

Congenital erythropietic porphyria has the following characteristics that are diagnostic even in early infancy:

Red urine in early infancy .

Photosensitivity

Hemolytic anemia

Splenomegaly

Erythrodontia of both deciduous and permanent teeth.

Coral red fluorescence of the teeth when exposed to Wood‘s light.

 

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.

 

ALKAPTONURIA AND OCHRONOSIS

This is a hereditary disease transmitted as an autosomal recessive gene, due to enzymatic defect in the metabolism of tyrosine and phenylalanin.

Clinical Manifestations.

Dark urine, which becomes later black due to increased homogentisic acid secretion in urine.

Deposition of brown-black pigment in the connective tissue.

In older age groups the manifestations are:

Pigmentation of the sclera, which is an early sign.

Deposition of pigment in the cartilage of the ears, nose and tendons of the extremities which may show blue, mottled brown macules.

Internal organs mainly great vessels, valves and larynx, genitalia may be also involved .

Arthropathy affecting the spinal joints , hips ,knees and shoulders.

 

ABNORMAL LIPID METABOLISMXANTHOMATOSIS

Xanthomatosis is accumulation of lipids in association of foam cells in the tissues.

Different clinical types.

Xanthelasma palpebrarum: this is the most common type of xanthomas affecting any age. Middle age women are the commonest to have this problem especially those who have biliary diseases. The lesions are yellowish plaques on the eyelids, which may coalesce to form large plaques.

Plane xanthomas: yellowish, raised papules, symmetrically distributed mainly on the eyelids sides of the neck and palms.

Eruptive xanthomas: yellow papules appear on the extensor surfaces of the limbs, joints and buttocks surrounded by a rim of erythema and may be tender. Eruptive xanthoma is associated by increased serum triglycerides .

Fig.354. Xanthomatoses Fig.355. Xanthomatoses

 

                                     

                                     Fig.355d. Xanthomatosis

                                              

                                Fig.355e. Xanthomatosis

 

 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.

Refsum‘s 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.

Various neurological changes occur, including deafness, cerebellar degeneration, polyneuropathy, and retinitis pigmentosa and cardiac abnormalities.

Refsum‘s syndrome can be diagnosed by lipid analysis of the blood or the skin. Normally no or very little phytanic acid is found in the blood (0-33 mumol/l).

Treatment

Treatment by a phytanic acid-free diet, in which green vegetables and dairy products are excluded, has been used. Plasma exchange in conjunction with diet.

   

ABNORMAL AMINO - ACIDS METABOLISM

These changes are recessively transmitted error of metabolism of amino acids leading to different skin manifestations. The skin manifestations depend on the specific amino-acid metabolism abnormality.

 

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.

 

LYSOSOMAL STORAGE DISEASE

These metabolic disorders are due to a defect in specific enzymes leading to accumulation of intermediary metabolic products in lysosomal organelles.

These syndromes include Hurler‘s syndrome, Chediak-Higash syndrome and others.

   

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.

 

ANDERSON‘S FABRY DISEASE(Lipoangiokeratoma)

This is a rare X linked recessive trait storage disorder leading to accumulation of ceramide trihexose in the tissues mainly in the endothelium of smooth muscles and blood vessels.

Clinical Manifestations

This syndrome has complex skin and systemic manifestations.

Skin manifestations begin to appear in the adult age in the form of dark blue or black lesions mainly on the back, abdomen, buttocks, umbilicus and mouth.

Systemic manifestations appear early in childhood in the form of weakness, malaise, cramps. In adult age, there is vague symptoms as fever after exercise with decreased sweating, neurological and psychological episodes and severe pain of the feet and hands.

Serious and even fatal complications in older age groups are due to cardiac, renal and cerebrospinal accidents.

 

MORQUIO AND HURLER SYNDROMES

Both of these syndromes are genetic diseases due to error of metabolism of mucopolysaccharides leading to greatly thickening of the skin due to deposit of mucopolysaccharides in tissues limiting joint movements.

  

REFERENCES

1. Elder GH. Recent advances in the identification of enzyme deficiencies in the porphyrias. Br J Dermatol 1983; 108: 729-34.

2. 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.

3. Moore MR, McColl KEL, Rimington C et al. Disorders of Porphyrin Metabolism. New York: Plenum Medical, 1987: 15.

4. Deybach JC, Grandchamp B, Grelier M et al. Prenatal exclusion of congenital erythropoietic porphyria (Gunther‘s disease) in a foetus at risk. Hum Genet 1980; 53: 217-21.

5. Nitowsky HM, Sassa S, Nakagawa A et al. Prenatal diagnosis of congenital erythropoietic porphyria. Pediatr Res 1978; 12: 455.

6. Moser HW, Moser AB, Chen WW et al. Ceramidase deficiency. Farber‘s lipogranulomatosis. In: Scriver CR et al., eds.

7. The Metabolic Basis of Inherited Disease 6th edn. New York: McGraw-Hill, 1989: 1645-54.

8. Barranger JA, Ginns EI. Glucogyl ceramide lipidoses: Gaucher‘s disease. In: Scriver CR et al., eds. The Metabolic Basis of Inherited Disease 6th edn. New York: McGraw-Hill, 1989: 1677-98.

9. Goldblatt J, Beighton P. Cutaneous manifestations of Gaucher disease. Br J Dermatol 1984; 111: 331-4.

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. Guthrie R, Susi A. A simple phenylalanine method for detecting phenylketonuria in large populations of newborn infants. Pediatrics 1963; 32: 338-43. 

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. Niederweiser A, Curtius H-CH. In: Bickel H, Wachtel H, eds. Inherited Diseases of Amino Acid Metabolism. New York: Thieme Verlag, 1985; 104.

15. Levy RI, Rifkind BM. Diagnosis and management of hyperlipo-proteineuria in infants and children. Am J Cardiol 1973; 31: 547-56.

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. Polano MK. Xanthomatosis and hyperlipoproteinaemia. Dermatologica 1974; 149: 1-9.18. Pucevich MV, Lataur DL, Bale G et al. Self-healing juvenile cutaneous mucinosis. J Am

Acad Dermatol 1984; 11: 327-32.19. Bonerandi J, Andrac L, Follana J et al. Self-healing juvenile cutaneous mucinosis. Ann

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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. Ljunghall K, Tjernlund U. Dermatitis herpetiformis: effect of gluten-restricted and

gluten-free diet on dapsone requirement and on IgA and C3 deposits in uninvolved skin. Acta Derm Venereol 1983; 63: 129.

Miller S. Nutritional deficiency and the skin. J Am Acad Dermatol 1989; 21: 1-