Skin Manifestations of Systemic Disease

This PatientPlus article is written for healthcare professionals so the language may be more technical than the condition leaflets. You may find the abbreviations list helpful.

Categorising the various types of cutaneous manifestations of systemic disease is not easy. The following therefore is a random list of diseases most commonly encountered in practice which 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

This can include pyoderma gangrenosum and erythema nodosum. Oral manifestations include aphthous stomatitis, mucosal nodularity (cobblestoning) and pyostomatitis vegetans (erythematous thickened mucosa). 2

Carcinoid syndrome

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

Diabetes mellitus

Recurrent skin infections are common, either due to fungi (e.g. genital candidiasis) or bacteria (e.g. folliculitis). Blisters on the feet may be found as may granuloma annulare.3 Brown macules sometimes develop on the shin; when these blister the condition is called bullosis diabeticorum.4 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 telangiectasia.

Liver disease

The cutaneous manifestations characteristically include:

Lichen planus is known to be linked to hepatitis C infection.5

Human immunodeficiency virus/acquired immunodeficiency syndrome

A variety of skin conditions can occur in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS):6

Dermatitis

The appearance can resemble psoriasis, Reiter's Disease or seborrheic dermatitis and has been termed 'psoriasiform dermatitis of AIDS'.6

Infections

Bacillary angiomatosis is a treatable infection caused by a rickettsia-like organism similar to Rochalimaea quintana, the agent of trench fever.7 Viral infections such as chronic herpes zoster can also occur.

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.8

Sarcoidosis9

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.

Mastocytosis10

This 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 commonest in babies. It can also cause urticaria pigmentosa either as skin wheals in infancy often following a bath, or extensive areas of dark brown macules that swell and go red when stroked in adults.

Amyloidosis11

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, 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.12 Cutaneous amyloidosis is associated with various autoimmune/immune disorders and associations with sarcoidosis and IgA nephropathy have been reported.13

Acromegaly

Cutaneous changes in acromegaly can include skin puffiness, oily skin with large pores, hypertrichosis, pigmented skin tags, acanthosis nigricans and psoriasis.14 Skin creases in the head area are deeper than normal (cutis verticis gyrata or 'Klingon head').15

Hypopituitarism

The skin is 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.16

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.

Hyperthyroidism

The skin in thyrotoxicosis is the obverse of that seen in myxoedema. It is warm and moist and flushing of the face and palms is sometimes seem. Pre-tibial myxoedema is characteristic.16

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 the axillae.16,17

Porphyria

There are a number of different forms of porphyria, e.g. porphyria cutanea tarda, erythropoietic porphyria. All are characterised by photosensitivity, with fragility and blistering of the skin when exposed to sunlight or ultraviolet rays.18,19

Rheumatoid arthritis20

Rheumatoid nodules - subcutaneous lumps seen near an affected joint - occur in about 25% of patients. 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 (palma 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.

Reiter's disease

Keratoderma blennorrhagicum is sometimes seen in this condition. 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.21

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.22


Document references

  1. Usatine RP; A cutaneous manifestation of a systemic disease. West J Med. 2000 Feb;172(2):84.
  2. Trost LB, McDonnell JK; Important cutaneous manifestations of inflammatory bowel disease. Postgrad Med J. 2005 Sep;81(959):580-5. [abstract]
  3. Bristow I; Non-ulcerative skin pathologies of the diabetic foot. Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S84-9. [abstract]
  4. Bullosis diabeticorum; Type 2 Diabetes Resource Centre eMedicine.com 2007; Pictures of bullosis
  5. Sanchez-Perez J, De Castro M, Buezo GF, et al; Lichen planus and hepatitis C virus: prevalence and clinical presentation of patients with lichen planus and hepatitis C virus infection. Br J Dermatol. 1996 Apr;134(4):715-9. [abstract]
  6. LeBoit PE; Dermatopathologic findings in patients infected with HIV. Dermatol Clin. 1992 Jan;10(1):59-71. [abstract]
  7. Bacillary Angiomatosis; Catalog of Clinical Images University of California 2007.; Picture of Bacillary Angiomatosis
  8. Fishman A, Sparano J; Kapsoi's Sarcoma eMedicine.com updated 2008.
  9. Jones JR, Parman CL; Cutaneous manifestation of a systemic disease. Am Fam Physician. 2004 Jan 1;69(1):145-6.
  10. Hogan D, Lewis VP; Macrocytosis eMedicine.com 2008.
  11. Chotzen V, Gandour-Edwards, R, Zang M et al; Long-term AL primary amyloidosis Dermatology Online Journal, December 1995 Volume 1, Number 2
  12. Alhaddab M, Srolovitz H, Rosen N; Primary systemic amyloidosis presenting as extensive cutaneous ulceration. J Cutan Med Surg. 2006 Sep-Oct;10(5):253-6. [abstract]
  13. Dahdah MJ, Kurban M, Kibbi AG, et al; Primary localized cutaneous amyloidosis: a sign of immune dysregulation? Int J Dermatol. 2009 Apr;48(4):419-21. [abstract]
  14. Ben-Shlomo A, Melmed S; Skin manifestations in acromegaly. Clin Dermatol. 2006 Jul-Aug;24(4):256-9. [abstract]
  15. Kuwahara RT, Swann M, Garcia C; "Klingon head". Cutis verticis gyrata. Am Fam Physician. 2005 Oct 1;72(7):1299-300.
  16. Jabbour SA; Cutaneous manifestations of endocrine disorders: a guide for dermatologists. Am J Clin Dermatol. 2003;4(5):315-31. [abstract]
  17. Cushing syndrome; DermNet NZ 2007
  18. Poh-Fitzpatrick, M, Elmets C; Porphyria Cutanea Tarda eMedicine.com 2008.
  19. Erythropoietic protoporphyria; DermNet NZ 2007
  20. Rheumatoid arthritis; DermNet NZ 2007
  21. Kataria RK, Brent LH; Spondyloarthropathies. Am Fam Physician. 2004 Jun 15;69(12):2853-60. [abstract]
  22. Dalamaga M, Karmaniolas K, Matekovits A, et al; Cutaneous manifestations in relation to immunologic parameters in a cohort of primary myelodysplastic syndrome patients. J Eur Acad Dermatol Venereol. 2008 May;22(5):543-8. Epub 2007 Dec 7. [abstract]

Acknowledgements

EMIS is grateful to Dr Laurence Knott for writing this article. The final copy has passed scrutiny by the independent Mentor GP reviewing team. ©EMIS 2009.
Document ID: 2785
Document Version: 21
Document Reference: bgp1006
Last Updated: 23 Jun 2009
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