A first impression of a patient’s skin can help guide the differential diagnosis and provide clues to the underlying diseases associated with cutaneous changes. Some findings may serve as early warning signs before organ-specific manifestations develop.

Paleness, for example, may indicate anemia, renal insufficiency, myxedema, or pituitary insufficiency, whereas cyanosis may result from heart disease. Skin redness may indicate secondary polycythemia or polycythemia vera. Facial flushing or redness may occur after alcohol consumption and may be associated with Cushing disease, hypertension, or mitral stenosis. Episodic flushing may indicate neuroendocrine tumors, pheochromocytomas, or mastocytosis.

Generalized erythema can occur in numerous infectious diseases, psoriasis, and paraneoplastic conditions. Brown skin discoloration may occur with Addison disease, hemochromatosis, or certain medications, while jaundice is associated with liver and biliary tract diseases. Ulceration may result from circulatory disorders associated with chronic venous insufficiency, peripheral arterial disease, diabetes mellitus, or pyoderma gangrenosum. Pyoderma gangrenosum may also prompt further evaluation for gastrointestinal, rheumatologic, and hematologic disorders.

Gastroenterology

• Celiac disease. Dermatitis herpetiformis (Duhring disease) is characterized by severe, burning pruritus. Recurrent crops of herpetiform papules and vesicles may develop on the buttocks, shoulders, extensor surfaces of the extremities, and scalp. Scratching can cause excoriations with serous to yellowish crusts and psoriasiform eruptions. Gluten is the primary trigger, and a strict gluten-free diet is the basis of treatment. Iodide can also exacerbate skin eruptions. Dapsone is used to control skin manifestations, particularly during the initial phase of dietary treatment. Skin findings may occur concurrently with or at a different time from those of gluten-sensitive enteropathy. Most patients with dermatitis herpetiformis also have some degree of gluten-sensitive enteropathy, although the gastrointestinal symptoms may be mild or absent.
• Inflammatory bowel disease. Crohn’s disease and ulcerative colitis may be associated with pyoderma gangrenosum, erythema nodosum, granulomatous lesions, cutaneous fistulas, abscesses, oral aphthae, and psoriasis.
• Whipple disease. This systemic disease is caused by the actinomycete bacterium Tropheryma whipplei and may be associated with genetic susceptibility and abnormalities in macrophage function. Skin manifestations include brown hyperpigmentation, erythema nodosum, and lichenoid eruptions.
• Pancreatitis. Localized inflammation of subcutaneous fat, known as panniculitis, can occur. Erythema nodosum is a common form of panniculitis. In severe pancreatitis, ecchymotic discoloration may occur with the Grey Turner, Cullen, and Fox signs, involving the flanks, periumbilical region, and upper thigh, respectively.
• Polyposis syndromes. Gastrointestinal polyps can occur with other findings, including neoplasms; pigment abnormalities; and hair, skin, and nail changes in Gardner syndrome, Cowden disease, Peutz-Jeghers syndrome, Muir-Torre syndrome, and Cronkhite-Canada syndrome. Disseminated, macular, and pinpoint hyperpigmentation of the lips can occur in Peutz-Jeghers syndrome, Laugier-Hunziker syndrome, LEOPARD syndrome, LAMB syndrome, and Carney complex.

Oncology

The Sister Mary Joseph nodule is a metastasis from gastrointestinal or gynecologic tumors, and less commonly, from pulmonary or urogenital tumors. These occur around the umbilicus. Carcinoid syndrome is characterized by flushing and telangiectasias caused by the release of vasoactive substances, including kallikrein, serotonin, histamine, and bradykinin, by neuroendocrine tumors. Thickened palmar creases, known as triple palms, and malignant acanthosis nigricans may occur. Malignant acanthosis nigricans is usually associated with gastrointestinal adenocarcinoma.

Erythema gyratum repens, characterized by migrating rings, occurs in lung, breast, and esophageal cancers. Paraneoplastic pemphigus, which involves the mucous membranes, is frequently associated with B-cell lymphomas. Bazex syndrome, also known as acrokeratosis paraneoplastica or acrokeratosis neoplastica syndrome, is associated with upper aerodigestive tract cancers, particularly pharyngeal and laryngeal cancers.

Hepatology

• Cirrhosis. Clinical findings may include atrophy and parchment-like skin, particularly on the hands, jaundice, palmar and plantar erythema, Dupuytren contracture, gynecomastia, spider nevi, and facial telangiectasias. The combination of these findings may provide clues to the underlying chronic liver disease. Hormonal changes can cause abdominal hair loss and gynecomastia in men. Portal hypertension can cause caput medusae on the abdomen. Generalized grey hyperpigmentation may occur in patients with chronic liver disease. Bronze diabetes is associated with hemochromatosis. Pruritus and nail changes, including leukonychia, flattened nails, rhagades at the corners of the mouth, and a glazed appearance of the lips and tongue, may also occur.
• Hepatitis. Striae distensae can occur in patients with chronic active hepatitis. Hepatitis B and C may be associated with leukocytoclastic vasculitis related to cryoglobulinemia, erythema nodosum, urticaria, erythema multiforme, polyarteritis nodosa, and porphyria cutanea tarda.

Cardiology

• Endocarditis. Petechiae occur in approximately 50% of cases. Painful Osler nodes may develop on the fingertips and toes, whereas painless, hemorrhagic Janeway lesions may appear on the palms and soles and measure up to 1 cm. Nonspecific subungual petechiae may also occur.
• Cardiac signs. Cyanosis with warm skin can occur in right-to-left shunts. Mitral facies, characterized by flushed cheeks and cyanosis of the lips, may occur with mitral valve stenosis. Clubbing of the fingers may also be present.
• Heart failure. Peripheral cyanosis with cold skin may occur. Other causes of acrocyanosis include pulmonary and autoimmune diseases, vasculitis, hyperglobulinemia, cryoglobulinemia, anorexia nervosa, medications, and toxins. Unlike Raynaud phenomenon, acrocyanosis is persistent and painless and does not cause ulcerations.
• Rheumatic and systemic diseases. Skin and cardiac manifestations may occur with rheumatic diseases, including polyarthritis, systemic lupus erythematosus, reactive arthritis (formerly known as Reiter syndrome), Behçet disease, scleroderma, dermatomyositis, polyarteritis nodosa, and rheumatic fever. Such manifestations may also occur in sarcoidosis, neurofibromatosis, tuberous sclerosis, diphtheria, gonococcal infection, and Kawasaki disease.

Nephrology

In chronic kidney disease or during long-term dialysis, the skin may appear pale because of renal anemia. Clay-brown skin discoloration caused by the simultaneous accumulation of melanin, carotenoids, and urochromogens may occur in advanced chronic kidney disease. Premature skin aging, including actinic elastosis, can also occur. Severe pruritus is a common condition. Distal reddish-brown nail discoloration with proximal white discoloration can produce a “half-and-half” appearance, also known as the Lindsay nail, a classic physical finding associated with chronic kidney disease.

Hematology

• Polycythemia vera. Livid facial discoloration and sudden generalized pruritus after contact with water may occur. Erythromelalgia is characterized by episodes of intense burning pain, erythema, and warmth in the hands or feet and is a recognized clinical manifestation of polycythemia vera.
• Porphyrias. Cutaneous porphyrias can cause bullous, vesicular, and erythematous skin lesions via phototoxic reactions associated with porphyrin accumulation. Porphyria cutanea tarda causes skin fragility and blistering, particularly in sun-exposed areas. Congenital erythropoietic porphyria, also known as Günther disease, is a rare genetic disorder that causes severe photosensitivity, skin fragility, and painful blistering. Erythropoietic protoporphyria typically causes painful photosensitivity, erythema, burning, and itching after exposure to sunlight. Acute intermittent porphyria and other acute hepatic porphyrias typically present with systemic, neurovisceral symptoms instead of cutaneous manifestations. These disorders should be distinguished from pseudoporphyria, a porphyria cutanea tarda-like blistering photodermatosis that can occur in individuals with chronic renal failure or those undergoing hemodialysis and may also be associated with certain medications. Pseudoporphyria occurs without the porphyrin abnormalities that define true porphyrias.

This story was translated from Univadis Germany, part of the Medscape Professional Network.