Contents << Previous Chapter Next Chapter >> Search

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.



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.



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 .



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.



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 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 .



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

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


Addison‘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 .



  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 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 .



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.

  1. Vasculitis

    Intestinal malabsorption may be associated with skin and bowel vasculitis.

  2. 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.



  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. 


Contents << Previous Chapter Next Chapter >> Search