Skin manifestations of systemic disease

What are skin manifestations?

The skin can be affected in a wide variety of underling conditions and it is always important to consider this possibility when a patient presents with any skin lesion that is not have a clear diagnosis such as dermatitis or psoriasis. This article provides an overview of some of the conditions most commonly encountered in practice which may manifest themselves by changes in the skin.

Hyperlipidaemia¹

Skin manifestations of hyperlipidaemia include flat yellow deposits around the eye (xanthelasmata). Elsewhere on the body they present as yellowish papules or nodules called xanthomata. Sudden eruptions can appear in large numbers over the buttocks, trunk and limbs, or a few larger lesions can develop on the elbows, knees, hands and over the Achilles tendon.

Gastrointestinal disease

Inflammatory bowel disease

Skin manifestations found in inflammatory bowel disease (Crohn's disease, ulcerative colitis) can include pyoderma gangrenosum and erythema nodosum.² Oral manifestations include aphthous stomatitis, mucosal nodularity (cobblestoning) and pyostomatitis vegetans (erythematous thickened mucosa).³

Carcinoid syndrome

Cutaneous metastases in carcinoid syndrome can present as deep nodules, hyperkeratosis and pigmentation changes similar to those seen in pellagra.⁴

Diabetes mellitus

Recurrent skin infections are common with diabetes mellitus, either due to fungi (eg, genital candidiasis) or bacteria (eg, folliculitis). Blisters and granuloma annulare may be found on the feet.⁵

Brown macules sometimes develop on the shin; when these blister, the condition is called bullosis diabeticorum.⁶ Necrobiosis lipoidica diabeticorum can also occur on the shins. The lesions have the appearance of plaques with dark red or purple edges, atrophic centres and surface telangiectasias.

Liver disease

The cutaneous manifestations characteristically include:

• Jaundice.

• Erythema of the palms.

• Purpura.

• Spider naevi.

• Generalised itching.

Lichen planus is known to be linked to hepatitis C infection.⁷

Human immunodeficiency virus/acquired immunodeficiency syndrome⁸

A variety of skin conditions can occur in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS).

Dermatitis

The appearance can resemble psoriasis, reactive arthritis or seborrhoeic dermatitis and has been termed 'psoriasiform dermatitis of AIDS'.

Infections

Bacillary angiomatosis is a treatable infection caused by a rickettsia-like organism similar to Rochalimaea quintana - the agent of trench fever. Viral infections such as chronic herpes zoster can also occur.⁹

Malignancy

Kaposi's sarcoma is an AIDS-defining illness characterised by initial bruise-like macules developing into brown-red or purple firm-to-hard nodules. In AIDS these are widespread, especially on the face and trunk.¹⁰

Sarcoidosis¹¹

Sarcoidosis can present with erythema nodosum, or with plaques, papules or nodules. The latter are commonly seen as smooth, dark brown/violaceous lesions arranged in an annular pattern. Infiltration of an old scar is characteristic so that it becomes brightly purple coloured. Lupus pernio is a slowly developing form that spreads into large areas of plaque on the chin and nose.

Mastocytosis¹²

Mastocytosis is a condition in which there is proliferation of mast cells. In the skin it can cause single or multiple, dark red nodules or plaques that develop into a blister or wheal when rubbed. This is at its most common in babies. It can also cause urticaria pigmentosa, either as skin wheals in infancy often following a bath, or as extensive areas of dark brown macules that swell and go red when stroked in adults.

Amyloidosis¹³

Amyloidosis appears in middle age with bruising, petechiae and purpura related to deposition of amyloid in the dermal blood supply. This is most frequently seen in the anogenital, periorbital and peri-umbilical regions, at the side of the neck and in the axillae. Atrophic waxy lesions with areas of purpura inside them may sometimes be seen, and the tips of the fingers may exhibit softening and loosening of the skin. A case of advanced primary amyloidosis presenting as a non-healing leg ulcer has also been reported.¹⁴

Cutaneous amyloidosis is associated with various autoimmune/immune disorders, and associations with sarcoidosis and IgA nephropathy have been reported.¹⁵

Acromegaly

Cutaneous changes in acromegaly can include skin puffiness, oily skin with large pores, hypertrichosis, pigmented skin tags, acanthosis nigricans and psoriasis.¹⁶ Skin creases in the head area are deeper than normal (cutis verticis gyrata, or 'Klingon head').¹⁷

Hypopituitarism¹⁸

In hypopituitarism the skin is often dry, scaly and puffy and the nails become brittle. The hair is coarse and sparse, especially in the axillae. Fine wrinkles around the eyes and mouth are typical.

Hypothyroidism¹⁹

In hypothyroidism the skin in myxoedema is cool to the touch, doughy, dry and puffy and there may be hair loss. Peri-orbital oedema may be accompanied by a yellowish colour to the skin.

Hyperthyroidism²⁰

In hyperthyroidism the skin is warm and moist and flushing of the face and palms is sometimes seem. Pretibial myxoedema is is an autoimmune manifestation of Graves' disease, but also occasionally occurs in Hashimoto's thyroiditis.

Cushing's syndrome

In Cushing's syndrome abdominal striae may be a prominent feature, caused by skin atrophy. The skin may bruise easily and skin infections and acne may be frequent problems. Skin darkening may occur in the palmar creases, on areas subject to pressure and in the axillae.¹⁸

Addison's disease²¹

Primary adrenal insufficiency (Addison's disease) causes hyperpigmentation, particularly evident in the buccal mucosa, lips, palmar creases, new scars and in areas subject to pressure such as elbows, knuckles and knees. The changes are not present in secondary adrenal insufficiency.

Porphyria

There are a number of different forms of porphyria - eg, porphyria cutanea tarda, erythropoietic porphyria.^{22 23} All are characterised by photosensitivity, with fragility and blistering of the skin when exposed to sunlight or ultraviolet rays.

Rheumatoid arthritis²⁴

Rheumatoid nodules - subcutaneous lumps seen near an affected joint - occur in about 25% of patients with rheumatoid arthritis. Other phenomena include thinning of the skin, translucency of the skin on the back of the hands, brittle nails which split lengthwise and reddened palms (palmar erythema). Dermatitis in which neutrophils are prominent on biopsy (neutrophilic dermatosis) may present as erythematous areas and interstitial granulomatous dermatitis is a rare condition in which rheumatoid papules may appear on the trunk. Cutaneous vasculitis may present as purpuric areas on the skin.

Reactive arthritis

Keratoderma blennorrhagicum is sometimes seen in reactive arthritis. It is characterised by hyperkeratotic lesions on the palms of the hands or the soles of the feet. Clear vesicles on an erythematous base develop which then progress to macules, papules and nodules. The lesions may be impossible to distinguish from pustular psoriasis.²⁵

Myelodysplastic syndrome

In myelodysplastic syndrome various cutaneous manifestations can occur, including leukaemia cutis, photosensitivity, prurigo nodularis and purpura. Cutaneous conditions are thought to indicate that the patient belongs to a high-risk group, associated with bone marrow transformation and hypergammaglobulinaemia.²⁶