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Skin manifestations of systemic disease

Medical Professionals

Professional Reference articles are designed for health professionals to use. They are written by UK doctors and based on research evidence, UK and European Guidelines. You may find one of our health articles more useful.

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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.


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.

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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.

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Liver disease

The cutaneous manifestations characteristically include:

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).


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


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


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


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.


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.


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


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


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.


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.


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.


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

Further reading and references

  1. Dwivedi S, Jhamb R; Cutaneous markers of coronary artery disease. World J Cardiol. 2010 Sep 26;2(9):262-9. doi: 10.4330/wjc.v2.i9.262.
  2. Ampuero J, Rojas-Feria M, Castro-Fernandez M, et al; Predictive factors for erythema nodosum and pyoderma gangrenosum in inflammatory bowel disease. J Gastroenterol Hepatol. 2014 Feb;29(2):291-5. doi: 10.1111/jgh.12352.
  3. Lankarani KB, Sivandzadeh GR, Hassanpour S; Oral manifestation in inflammatory bowel disease: a review. World J Gastroenterol. 2013 Dec 14;19(46):8571-9. doi: 10.3748/wjg.v19.i46.8571.
  4. Shah KR, Boland CR, Patel M, et al; Cutaneous manifestations of gastrointestinal disease: part I. J Am Acad Dermatol. 2013 Feb;68(2):189.e1-21; quiz 210. doi: 10.1016/j.jaad.2012.10.037.
  5. Bristow I; Non-ulcerative skin pathologies of the diabetic foot. Diabetes Metab Res Rev. 2008 May-Jun;24 Suppl 1:S84-9.
  6. Ghosh SK, Bandyopadhyay D, Chatterjee G; Bullosis diabeticorum: A distinctive blistering eruption in diabetes mellitus. Int J Diabetes Dev Ctries. 2009 Jan;29(1):41-2. doi: 10.4103/0973-3930.50714.
  7. Halawani M; Hepatitis C virus genotypes among patients with lichen planus in the Kingdom of Saudi Arabia. Int J Dermatol. 2014 Feb;53(2):171-7. doi: 10.1111/j.1365-4632.2012.05685.x. Epub 2013 May 15.
  8. Chawhan SM, Bhat DM, Solanke SM; Dermatological manifestations in human immunodeficiency virus infected patients: Morphological spectrum with CD4 correlation. Indian J Sex Transm Dis. 2013 Jul;34(2):89-94. doi: 10.4103/0253-7184.120538.
  9. Keong SC, Fu GW, Hashim H; Cutaneous lesions of bacillary angiomatosis. Rev Soc Bras Med Trop. 2022 Aug 12;55:e0101. doi: 10.1590/0037-8682-0101-2022. eCollection 2022.
  10. Cedeno-Laurent F, Gomez-Flores M, Mendez N, et al; New insights into HIV-1-primary skin disorders. J Int AIDS Soc. 2011 Jan 24;14:5. doi: 10.1186/1758-2652-14-5.
  11. Haddad N, de Oliveira Filho J, Nasser Kda R, et al; Musculoskeletal and cutaneous sarcoidosis: exuberant case report. An Bras Dermatol. 2014 Jul-Aug;89(4):660-2.
  12. Barnes M, Van L, DeLong L, et al; Severity of cutaneous findings predict the presence of systemic symptoms in pediatric maculopapular cutaneous mastocytosis. Pediatr Dermatol. 2014 May-Jun;31(3):271-5. doi: 10.1111/pde.12291. Epub 2014 Feb 26.
  13. Kumar S, Sengupta RS, Kakkar N, et al; Skin involvement in primary systemic amyloidosis. Mediterr J Hematol Infect Dis. 2013;5(1):e2013005. doi: 10.4084/MJHID.2013.005. Epub 2013 Jan 2.
  14. 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.
  15. 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.
  16. Ben-Shlomo A, Melmed S; Skin manifestations in acromegaly. Clin Dermatol. 2006 Jul-Aug;24(4):256-9.
  17. Kuwahara RT, Swann M, Garcia C; "Klingon head". Cutis verticis gyrata. Am Fam Physician. 2005 Oct 1;72(7):1299-300.
  18. Jabbour SA; Cutaneous manifestations of endocrine disorders: a guide for dermatologists. Am J Clin Dermatol. 2003;4(5):315-31.
  19. Keen MA, Hassan I, Bhat MH; A clinical study of the cutaneous manifestations of hypothyroidism in kashmir valley. Indian J Dermatol. 2013 Jul;58(4):326. doi: 10.4103/0019-5154.113951.
  20. Puri N; A study on cutaneous manifestations of thyroid disease. Indian J Dermatol. 2012 May;57(3):247-8. doi: 10.4103/0019-5154.96227.
  21. Addison disease; DermNet
  22. Munoz-Santos C, Guilabert A, Moreno N, et al; Familial and sporadic porphyria cutanea tarda: clinical and biochemical features and risk factors in 152 patients. Medicine (Baltimore). 2010 Mar;89(2):69-74. doi: 10.1097/MD.0b013e3181d50928.
  23. Katugampola RP, Badminton MN, Finlay AY, et al; Congenital erythropoietic porphyria: a single-observer clinical study of 29 cases. Br J Dermatol. 2012 Oct;167(4):901-13. doi: 10.1111/j.1365-2133.2012.11160.x. Epub 2012 Sep 18.
  24. Clarke JT, Werth VP; Rheumatic manifestations of skin disease. Curr Opin Rheumatol. 2010 Jan;22(1):78-84. doi: 10.1097/BOR.0b013e328333b9e2.
  25. Naik HB, Cowen EW; Autoinflammatory pustular neutrophilic diseases. Dermatol Clin. 2013 Jul;31(3):405-25. doi: 10.1016/j.det.2013.04.001. Epub 2013 Jun 2.
  26. 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.

Article History

The information on this page is written and peer reviewed by qualified clinicians.

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