Abnormal Findings on the Hands: Clues to Systemic Disease

Lesions on the dorsal aspect of the hand, demonstrating the photodistribution of Dermatomyositis, are shown. Note the sparing of the interdigital web spaces.

Dermatologic manifestations of systemic disease have long been known and span a range from the subtle to the conspicuous. Of these, a number feature prominently on the hands.

Gottron papules are polygonal, flat-topped, pink papules of the knuckles associated with dermatomyositis, an idiopathic inflammatory myopathy with characteristic cutaneous findings.

Another example of Gottron papules is shown.

Dermatologic manifestations are only one of a set of features of dermatomyositis, a systemic disorder that also frequently affects the joints, the esophagus, the lungs, and, less commonly, the heart. Patients with cutaneous manifestations of dermatomyositis may also have an associated systemic malignancy, and age-appropriate cancer screening is recommended.

The violaceous "heliotrope" rash on the eyelids is another characteristic and possibly pathognomonic cutaneous feature of dermatomyositis. It is closely associated with underlying muscle disease, especially when the overlying skin lacks scale and lichenification.

A hand with Raynaud phenomenon is shown. Notice the discoloration of the fingers.

Raynaud phenomenon manifests as recurrent vasospasm of the fingers and toes, usually in response to stress or exposure to cold. Secondary Raynaud phenomenon should be distinguished from primary Raynaud phenomenon (Raynaud disease). They are distinct disorders that share a similar name. Raynaud disease is characterized by the occurrence of the vasospasm alone, with no association with another illness. Secondary Raynaud phenomenon is a designation usually used in the context of vasospasm associated with another illness, most commonly an autoimmune disease. Image courtesy of Wikipedia Commons.

Secondary Raynaud phenomenon in a patient with systemic sclerosis is shown.

Raynaud phenomenon is a common finding in this systemic connective tissue disease. There is symmetrical acral vasospasm, with characteristic pallor, cyanosis, and suffusion. Patients with Raynaud phenomenon also often note a sense of fullness and tautness.

Sclerosis of the hands, a common presentation in progressive systemic sclerosis is shown.

Characteristics of systemic sclerosis include essential vasomotor disturbances; fibrosis; subsequent atrophy of the skin, subcutaneous tissue, muscles, and internal organs (eg, gastrointestinal tract, lungs, heart, kidney, central nervous system); and immunologic disturbances. Generally, renal and lung changes are responsible for death in patients with systemic sclerosis. Image courtesy of Wikimedia Commons.

The digital pits of systemic sclerosis are ischemic in nature and typically are intensely painful. They commonly become colonized with staphylococci or enteric bacilli.

Although not in the hand, other classic findings of systemic sclerosis include thickened and taut skin with numerous telangiectasias. Radical furrowing around the mouth is characteristic in the later stage of the disease. Patients with systemic sclerosis may be at increased risk for malignancy, including breast carcinoma; multiple myeloma; lymphoma; and cancer of the ovary, esophagus, colon, or rectum.

Subungual (splinter) hemorrhages (arrow) -- dark red linear lesions in the nailbeds -- are common in subacute infective endocarditis, but may also be seen in patients with vasculitis or be secondary to trauma.

Osler nodes (arrow), another finding related to subacute infective endocarditis, are smallish, tender, subcutaneous nodules that range from red to purple and are found primarily in the pulp spaces of the terminal phalanges of the fingers and toes, soles of the feet, and the thenar and hypothenar eminences of the hands. Their appearance is often preceded by neuropathic pain. They last from hours to several days. The underlying mechanism is probably the circulating immunocomplexes of subacute infective endocarditis.

In contrast, Janeway lesions are nontender maculae on the extremities, especially on toes and the soles of the feet, but also on fingers and palms of the hands. They are retiform purpura caused by septic emboli in acute infective endocarditis.

Necrotizing vasculitis may be seen in the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and septic vasculitis. Patients present with digital infarction or retiform purpura.

Retiform purpura is shown.

The ANCA-associated vasculitides include Wegener granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome.

Thick, doughy skin with blisters and milia are characteristic of porphyria cutanea tarda, a term encompassing a group of familial (20%) and acquired (80%) disorders in which activity of the heme synthetic enzyme uroporphyrinogen decarboxylase is deficient.

Porphyria cutanea tarda is commonly associated with hepatitis C infection and may be seen in heterozygotes for the hemochromatosis gene.

The most common presenting sign of porphyria cutanea tarda is fragility of sun-exposed skin after mechanical trauma, leading to erosions and bullae, typically on hands and forearms and occasionally on face or feet. Healing of crusted erosions and blisters leaves milia, hyperpigmented patches, and hypopigmented atrophic scars. Ethanol intake, estrogen therapies, and HIV infection are among other factors that may contribute to the development of porphyria cutanea tarda.

This slide demonstrates palmar erythema in a patient with hepatitis C virus (HCV) infection.

Palmar erythema may be seen in patients with liver dysfunction, such as chronic hepatitis. Cutaneous findings relevant to HCV infection manifest in 20%-40% of patients presenting to dermatologists and in a significant percentage (15%-20%) of general patients. HCV must be considered in the differential diagnosis of these patients. Other cutaneous manifestations of HCV include mixed cryoglobulinemia, leukocytoclastic vasculitis, lichen planus, and sicca syndrome, all of which should be regarded as early markers of a potentially fatal chronic liver disease. Image courtesy of Walter Reed Army Medical Center Dermatology.

Pinch purpura are a characteristic presenting finding in patients with systemic amyloidosis. Pinch purpura may be precipitated by minor trauma; the face is affected most commonly, especially the eyelids and periorbital area ("raccoon eyes" sign).

Xanthomas over joints (tuberous xanthomas) are common in type 2 hypercholesterolemia, but tendinous xanthomas are more specific for the homozygous familial hypercholesterolemia (FH). Patients with homozygous FH may have cutaneous xanthomas at birth or by early childhood. Tuberous xanthomas may also appear on elbows or knees.

Metacarpophalangeal joint tendon xanthomas in a 45-year-old man with heterozygous FH are shown.

Most children with heterozygous FH do not develop tendon xanthomas or corneal arcus. By the third decade of life, more than 60% of patients with untreated FH develop tendon xanthomas.

Herpetic whitlow (vesicular outbreaks on the hands and the digits) in a young child is shown.

Herpetic whitlow is most commonly due to infection by herpes simplex virus (HSV)-1. It usually occurs in children who suck their thumbs. Herpetic whitlow due to HSV-2 is increasingly recognized and is probably due to digital-genital contact. Image courtesy of Wikimedia Commons.

A transverse palmar crease (simian crease) in a child with Down syndrome is shown. This finding is seen in 40%-50% of patients with Down syndrome.

Other common cutaneous findings in Down syndrome include soft and velvety skin in early childhood, dry skin in late childhood (xerosis, atopic dermatitis, palmoplantar hyperkeratosis, and seborrheic dermatitis), premature wrinkling of the skin, cutis marmorata, and acrocyanosis

Arachnodactyly -- abnormally long and slender fingers in comparison to the palm -- in a patient with Marfan syndrome (right) is shown.

Arachnodactyly is a common feature of Marfan syndrome, in addition to disproportionately long limbs in comparison with the trunk.

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• Cutaneous Manifestations of Systemic Diseases
• Diseases of the Nails
• Fingernail Abnormalities: Vital Clues to Patient Health
• The Many Faces of Eczema
• Which Rashes to Worry About
• Other Slideshows

For more information, see the following resources:

• Medscape Reference: Addison Disease
• Medscape Reference: Cutaneous Manifestations of Hepatitis C
• Medscape Reference: Dermatologic Manifestations of Down Syndrome
• Medscape Reference: Dermatologic Manifestations of Herpes Simplex
• Medscape Reference: Dermatomyositis
• Medscape Reference: Familial Hypercholesterolemia

For more information, see the following resources:

• Medscape Reference: Genetics of Marfan Syndrome
• Medscape Reference: Infective Endocarditis
• Medscape Reference: Porphyria Cutanea Tarda
• Medscape Reference: Primary Systemic Amyloidosis
• Medscape Reference: Raynaud Phenomenon
• Medscape Reference: Systemic Sclerosis

Contributor Information

Authors
Carly A. Elston
Medical Student
The Commonwealth Medical College
Scranton, Pennsylvania

Disclosure: Carly A. Elston has disclosed no relevant financial relationships.

Dirk M. Elston, MD
Director
Ackerman Academy of Dermatopathology
New York, New York

Disclosure: Dirk M. Elston, MD, has disclosed no relevant financial relationships.

Nazanin Saedi, MD
Dermatology Fellow
SkinCare Physicians
Chestnut Hill, Massachusetts

Disclosure: Nazanin Saedi, MD, has disclosed no relevant financial relationships.

Contributor Information

Editor
Lars Grimm, MD, MHS
House Staff
Department of Diagnostic Radiology
Duke University Medical Center
Durham, North Carolina

Disclosure: Lars Grimm, MD, MHS, has disclosed no relevant financial relationships.

Reviewer
Rashid M. Rashid, MD
Resident Physician
Department of Dermatology
University of Texas
MD Anderson Cancer Center
Morzak Research Initiative
Houston, Texas

Disclosure: Rashid M. Rashid, MD, has disclosed no relevant financial relationships.

Suggested Reading

• Carlson JA. The histological assessment of cutaneous vasculitis. Histopathology. 2010;56:3-23.
• Cassiman D, Vannoote J, Roelandts R,et al. Porphyria cutanea tarda and liver disease. A retrospective analysis of 17 cases from a single centre and review of the literature. Acta Gastroenterol Belg. 2008;71:237-242.
• Englander L, Friedman A. Iron overload and cutaneous disease: an emphasis on clinicopathological correlations. J Drugs Dermatol. 2010;9:719-722.
• Fargion S, Fracanzani AL. Prevalence of hepatitis C virus infection in porphyria cutanea tarda. J Hepatol. 2003 ;39:635-638.
• Frank J, Poblete-Gutiérrez P. Porphyria cutanea tarda--when skin meets liver. Best Pract Res Clin Gastroenterol. 2010;24:735-745.
• Gisbert JP, García-Buey L, Pajares JM, Moreno-Otero R. Prevalence of hepatitis C virus infection in porphyria cutanea tarda: systematic review and meta-analysis. J Hepatol. 2003;39:620-627.
• Leung A, Sung CB, Kothari G, Mack C, Fong C. Utilisation of plasma exchange in the treatment of digital infarcts in Wegener's granulomatosis. Int J Rheum Dis. 2010;13:e59-e61. doi: 10.1111/j.1756-185X.2010.01541.x.
• Mehrany K, Drage LA, Brandhagen DJ, Pittelkow MR. Association of porphyria cutanea tarda with hereditary hemochromatosis. J Am Acad Dermatol. 2004;51:205-211.
• Nagai Y, Shimizu A, Suto M, et al. Digital gangrene in systemic lupus erythematosus. Acta Derm Venereol. 2009;89:398-401.

Suggested Reading

• Sams H, Kiripolsky MG, Bhat L, Stricklin GP. Porphyria cutanea tarda, hepatitis C, alcoholism, and hemochromatosis: a case report and review of the literature. Cutis. 2004;73:188-190. Review.
• Soyfoo MS, Couturier B, Cogan E. Cryofibrinogenaemia with vasculitis: a new overlap syndrome causing severe leg ulcers and digital necrosis in rheumatoid arthritis? Rheumatology (Oxford). 2010;49:2455-2457. Epub 2010 Jul 20.
• Todoli Parra JA, Hernández MM, Arrébola López MA. Efficacy of bosentan in digital ischemic ulcers. Ann Vasc Surg. 2010;24:690.e1-34.
• Van Meter JR, Tierney KR, Pittelkow MR. Iron, genes, and viruses: the porphyria cutanea tarda triple threat. Cutis. 2011;88:73-76.
• Young LC. Porphyria cutanea tarda associated with Cys282Tyr mutation in HFE gene in hereditary hemochromatosis: a case report and review of the literature. Cutis. 2007;80:415-418.