• drug eruptions
• skin signs of internal malignancy
• skin signs of internal disease

other than malignancy

• Urticaria
• Morbilliform
• Fixed drug eruption
• Erythema multiforme
• Stevens-Johnson Syndrome
• Toxic epidermal necrolysis

Urticaria (hives)

• Drugs (e.g., penicillins) are a common cause of urticaria, but urticaria can be precipitated by other internal and external factors
• Primary lesion is a wheal, a flesh-colored to pink, well circumscribed plaque caused by dermal edema; itchy!
• Individual lesions last only a few hours, never more than 24 hours
• When caused by drugs, may be IgE mediated, triggering mast cell granule release; or drug may directly cause mast cell granule release

Morbilliform eruption
(exanthematous drug eruption, maculopapular drug eruption):
 

• "morbilliform" refers to a resemblance to the rash of measles (morbilli is Latin for measles); measles is a rare disease now, but morbilliform eruptions are common

• a morbilliform eruption is symmetrically distributed on the trunk and proximal extremities, and consists of bright pink macules and slightly raised papules ("maculopapular")

Fixed drug eruption

• "fixed" in that it occurs at same sites with each episode
• OTC drugs containing phenolphthalein, pseudoephedrine, etc. common culprits
• tetracyclines, barbiturates, phenothiazines, sulfonamides
• oval, itchy or burning dusky red plaque

Erythema multiforme

• a form of cutaneous reaction to an underlying condition. In 50% of cases, a cause can’t be identified
• common causes: drugs (sulfonamides, phenytoin, barbiturates, penicillin, etc.); infections (esp. herpes simplex and Mycoplasma); inflammatory bowel disease
• eruption usually lasts for a week or two, then spontaneously remits
• the "target" lesion is approximately 1cm dull-red macule or papule with a central area of blistering or hemorrhage

• severe erythema multiforme affecting mucous membranes as well as skin is called "Stevens-Johnson syndrome"

Toxic epidermal necrolysis (TEN)

• it is unclear whether TEN is a severe form of erythema multiforme or a distinct disease
• 80% of cases have a strong association with a specific drug (list is similar to that for erythema multiforme)
• TEN is a medical emergency, on the order of a total body burn

• cutaneous metastases
• paraneoplastic syndromes
• heritable "cancer syndromes"

Sister Mary Joseph nodule

• umbilical metastasis; poor prognosis
• precedes or follows diagnosis of CA
• CA sites (decreasing order of frequency): colon, ovary, pancreas, endometrium, breast, small bowel

Paraneoplastic Syndromes

The skin often presents a clue that an internal malignancy is present. The combination of a malignancy and associated signs and symptoms that are seemingly unrelated to the actual tumor is called a "paraneoplastic" syndrome.
 

Erythema gyratum repens

• "wood-grain" pattern
• wavy, erythematous, urticarial bands with scale

• slowly migrate
• breast, stomach, bladder, prostate, cervix; occasionally no CA

Glucagonoma syndrome -- necrolytic migratory erythema

• alpha cell tumor of the pancreas; occasionally no neoplasm found
• abdomen, thighs and buttocks
• patchy erythema with flaccid vesicles and bullae
• glossitis, angular cheilitis, normocytic anemia, low amino acid levels in serum

Sweet’s syndrome (acute febrile neutrophilic dermatosis)

• painful red plaques and papules - face, neck, upper chest, arms, legs
• usually females (4:1); fever, leukocytosis prominent
• Associations, benign: URIs, strep, RA, Crohns, sarcoidosis, Behcet’s, pregnancy
• Association, malignant: AML, myelodysplasis, lymphoma--may follow by months to years
• Rx: prednisone

Trousseau’s sign

• superficial migratory thrombophlebitis and neoplasia
• 75% of CA in pancreas, stomach, lung, prostate, hematopoietic
• hypercoagulable state; thrombophlebitis resistant to therapy--sustained low grade DIC

Pancreatic panniculitis

• Fat necrosis, fever, eosinophilia, joint pain
• Pancreatic CA; also acute or chronic pancreatitis
• Circulating lipases and amylase
• Tender red nodules stimulating erythema nodosum

heritable "cancer syndromes"

• Peutz-Jehger
• Torre
• Cowden’s
• etc.

• Multiple hamartomatous polyps in small bowel (most common), stomach and colon; low risk of bowel malignancy
• multiple lentigines (freckle-like) of lips, nose, oral mucosa, fingertips and nail beds
• non-intestinal malignancies increased: lung, ovary, endometrium pancreas, myeloma

Torre syndrome

• autosomal dominant; "cancer-family" syndrome
• multiple low-grade malignancies of the GI and GU tracts; occasionally breast, lymphoma; multiple GI polyps in 25%
• sebaceous neoplasms: adenomas, carcinomas, sebaceous BCCs

Pyoderma gangrenosum

• characteristic rapidly expanding ulcer with bluish undermined border; often lower extremities; begin as sterile pustules
• 50% no disease association
• 1% to 10% of patients with active ulcerative colitis; often (but not always) parallels disease
• Other disease associations: Crohn’s, chronic active hepatitis, rheumatoid arthritis, HIV infection; acute and chronic granulocytic leukemia (bullous PG)
• can be associated with underlying malignancy (leukemia, etc.)

Cullen’s sign

• Periumbilical purpura associated with acute pancreatitis
• hematomas dissect along fascial plans from the retroperitoneal site of bleeding to the periumbilical area
• Turner’s sign--purpura of the left flank; same cause

Porphyria cutanea tarda

• most common porphyria; sporadic>80%; autosomal dominant in remainder
• photosensitivity; skin fragility with blistering, scarring and milia
• facial hypertrichosis; scleroderma-like change

Porphyria cutanea tarda (cont.)

• defect: uroporphyrin decarboxylase in liver and erythroctyes; increased iron stores
• ETOH, estrogen, iron, hexachlorobenzene toxicity
• Rx: phlebotomy, antimalarials

Xanthomas

• may be a sign of systemic metabolic abnormality or a local cellular dysfunction
• xanthomas may be the first sign of one the hyperlipoproteinemias, rare but serious metabolic diseases
• xanthelasma are xanthomas of eyelids that may or may not be associated with hyperlipidemia

• eruptive xanthomas, tendon xanthomas, and tuberous xanthomas are signs of significant hyperlipidemia; these patients require careful evaluation and prompt treatment

extensor tendons of fingers, patella, elbows, Achilles tendon (one of the most common sites); diffuse infiltration of tendon by lipid

• hypercholesterolemia; Types II and III
• normal lipids: cerebrotendinous xanthomatosis; plant sterols

tuberous xanthomas
 

lipid deposits in the dermis and subcutis; papuler, nodular or plaques; extensor surfaces of large joints, hands, buttocks, heels, flexures

• familial or acquired hypertriglyceridemias; biliary cirrhosis

other xanthomas

• usually abrupt increase in serum triglyceride levels

• familial type III and type IV

• velvety thickening and darkening (hyperpigmentation) of the skin, especially on the nape of the neck, axillae and other body folds

• underlying causes may be hereditary or acquired, and include:
• obesity; drugs; "malignant" acanthosis nigricans; hereditary, benign AN
• hyperinsulinemia is a common denominator

Erythema nodosum

• deep erythematous painful nodules, symmetrically on the lower legs; female predominance; a hypersensitivity panniculitis
• fever, chills, malaise, leukocytosis
• disease associations: streptococcal infections, drugs (OCPs, sulfonamides, iodides), pregnancy, TB, deep mycoses, acute sarcoidosis, inflammatory bowel disease

Telogen effluvium

• a distinctive form of hair loss that is a response to an underlying systemic condition
• normally, about 50-100 telogen hairs are shed from the scalp each day; in telogen effluvium, this number is greatly increased
• the telogen hairs start falling out about 3 months after a "precipitating event--" major surgery, severe illness, certain drugs, and childbirth being the most common. Chronic disease or drug ingestion can cause a sustained telogen effluvium--e.g., hypothyroidism, retinoid use.

Erythema chronicum migrans (erythema migrans)

• often the first manifestation of Lyme disease = Lyme borreliosis
• spirochete Borrelia burgdorferi is transmitted by the bite of the deer tick Ixodes scapularis in the northeastern U.S. (other species elsewhere)
• systemic borreliosis is a potentially serious disease, causing both acute and chronic symptoms such as fever, malaise, arthralgia, carditis, arthritis, meningitis, etc.

Erythema chronicum migrans (erythema migrans)

• typical lesion is a macule or papule that expands over several days, with central clearing, to form an annular, erythematous patch or plaque; may reach 15 or more CM in size
• soldiers and Marines hiking through fields in endemic areas are prone to this disease

• DLE may be one of several cutaneous findings seen in systemic lupus erythematosus
• note: DLE often occurs as an isolated finding, not associated with SLE
• sharply marginated, scaly, atrophic, red plaques; round, oval or polycyclic
• more common in young adult women, somewhat more common in African-Americans
• exposed areas of body: face, scalp, ears, hands, forearms

Leukocytoclastic vasculitis (LCV)

• clinically causes "palpable purpura," small, raised areas of cutaneous hemorrhage and inflammation at the site of venular destruction
• may be associated with fever, joint pain, and internal organ damage (kidneys, GI tract, brain)
• lesions are usually numerous and tend to affect the legs and ankles most severely 

• multiple underlying "causes" can precipitate LCV:
• drugs, such as sulfonamides, penicillins, others
• infections, such as Group A streptococcal, viral hepatitis (e.g. Hep. C), others
• immunologic diseases such as systemic lupus erythematosus, rheumatoid arthritis, cryoglobulinemia
• neoplasms such as lymphomas
• idiopathic--no cause found in @50% of cases

• triad of oral and genital ulcerations and inflammatory eye disease
• males 2:1; HLA-B5 increased in some populations
• onset with aphthous ulcers and ulcers of scrotum or labia
• fever, malaise, arthralgia, iritis, uveitis
• pathergy; erythema nodosum; thrombophlebitis; CNS disease--poor prognosis

• post-venereal and post-enteric; HLA-B27
• urethritis, conjunctivitis, iritis, arthritis
• skins lesions: keratoderma blenorrhagicum (keratotic conical lesions on lateral and palmoplantar aspects of hands and feet)
• circinate balanitis--annular erythematous lesions on glans penis
• psoriasiform lesions on scrotum, buttocks, trunk, extremitis, scalp
• marked nail dystrophy, painful erythema of fingers and toes