Gastroenterology and Hepatology Board Review: Pearls of Wisdom, Third Edition
Section IX MISCELLANEOUS TOPICS
CHAPTER 58. Gastrointestinal and Liver Dermatoses
Michelle O. DiBaise, PA-C, MPAS, DFAAPA
What are the four D’s of pellagra?
1. Dermatitis (photosensitive)
A deficiency in what nutrients may cause pellagra?
• Niacin (most commonly)
What other causes of pellagra exist?
• Alterations in tryptophan metabolism secondary to carcinoid
• Chronic alcoholism
• Chronic colitis
• Chronic dialysis
• Cirrhosis of the liver
• Prolonged diarrhea
• Tuberculosis of the GI tract
• HIV infection
• Hartnup’s disease
• Use of isoniazid, 5-fluorouracil, 6-mercaptopurine, or sulfapyridine
Vitiligo has been associated with what nutritional deficiencies?
• Vitamin B12
• Folic acid
• Vitamin C
What disease/nutritional deficiency leads to perifollicular purpura?
Scurvy/vitamin C deficiency. Other findings include poor wound healing, corkscrew hairs, and gingival bleeding.
What percent of patients with the type of neurocutaneous porphyria shown in the figure will develop hepatic cirrhosis?
Two to five percent of patients with erythropoeitic protoporphyria (EPP) will develop cirrhosis. The enzyme defect responsible for EPP is ferrochelatase.
Plummer–Vinson syndrome is associated with what findings?
• A postcricoid web
• Koilonychia (“spoon nails”)
• Angular stomatitis
• Sore tongue
• Iron deficiency
What percent of patients with Plummer–Vinson syndrome are at risk of developing a carcinoma?
Between 3% and 15% will develop squamous cell carcinoma at the site of the postcricoid web. Patients with coexisting celiac disease may be at an even greater risk. There is a rare association of Plummer–Vinson syndrome with gastric carcinoma particularly in patients with previous gastric surgery.
What is the classical dermatologic finding in patients with hemochromatosis?
Bronze to metallic gray pigmentation of the skin.
What autosomal recessive condition leads to a perioral, acral and genital eczematous eruption, alopecia, glossitis, and diarrhea?
What is the underlying nutritional cause of acrodermatitis enteropathica?
What skin reactions are found in PCT?
• Vesicles/bullae on dorsa of hands/feet
• Skin fragility/scarring
• Sclerodermoid plaques
• Milia on fingers/hands
The enzyme defect responsible in PCT is uroporphyrinogen decarboxylase.
A 39-year-old man with a long history of recurrent epistaxis presents with melena. The oro-labial lesions demonstrated in the figure are noted. What is the most likely diagnosis?
Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome).
Treatment for the condition illustrated in the figure includes what modalities?
The lesion is pyoderma gangrenosum. Treat the underlying disorder, if one exists (40%–50% of cases are idiopathic). Surgical debridement should be avoided as it can stimulate the development of new lesions. Other treatment options include:
• Systemic glucocorticoids
What genetic mutation is responsible for inherited acrodermatitis enteropathica?
SLC39A4 gene located on band 8q24.3 that encodes a transmembrane protein required for zinc uptake and is expressed on the enterocytes of the duodenum and jejunum.
A 59-year-old woman with diabetes mellitus presents with bilateral, symmetrical, pruritic vesicles on the elbows, knees, buttocks, and lower back. A skin biopsy reveals granular dermal papillary deposits of IgA. What is the diagnosis?
A 27-year-old man presented for sigmoidoscopy because of intermittent hematochezia. Numerous polyps were seen. A peculiar freckling pattern on his lips was also noted. What is the most likely diagnosis?
A 72-year-old woman presents with periorofacial, intertriginous, and perigenital circinate lesions with vesicles, crusting, and postinflammatory pigmentation in association with glossitis, weight loss, diarrhea, and diabetes. The rash is shown below. What is the diagnosis?
Glucagonoma. It arises in the islet cells of the pancreas and is associated with a distinctive dermatitis referred to as necrolytic migratory erythema (NME), which is histologically similar to acrodermatitis enteropathica. Since the rash of NME may be an early sign in slow-growing tumors, this differential should be kept in mind.
What gastrointestinal (GI) conditions may lead to acquired zinc deficiency?
• Chronic inflammatory bowel disease (IBD) with diarrhea and/or malabsorption
• Pancreatic insufficiency
• Surgically induced conditions such as short bowel syndrome
What are the cutaneous manifestations of hepatitis C?
• Lichen planus
• Porphyria cutanea tarda (PCT)
• Leukocytoclastic vasculitis/cryoglobulinemia
• Sialadenitis/sicca syndrome
• Corneal ulceration
• Pruritis with excoriations
• Erythema nodosum (EN)
• Erythema multiforme (EM)
• Polyarteritis nodosa
What condition is associated with the nail changes illustrated in the figure below?
Cirrhosis. Skin and nail findings associated with cirrhosis include:
• White nails referred to as Terry’s nails
• Spider nevi
• Diffuse muddy gray color of the skin or a blotchy brown pigmentation
• Linear pigmentation in skin creases
• Perioral and periorbital hyperpigmentation (chloasma hepaticum)
• Guttate hypomelanosis
• Palmar erythema
• Portal-systemic collaterals over the abdomen
• Decrease in facial and body hair growth
What percent of PCT patients have associated chronic hepatitis C?
What cutaneous side effects are seen with interferon- therapy?
• Lupus-like illness
• Systemic sclerosis
• Idiopathic thrombocytopenic purpura
What diagnoses should be considered when there are skin findings consistent with PCT in addition to acute episodes of abdominal pain, nausea, vomiting, paralysis, and seizures?
• Variegate porphyria (VP) (most common in South Africans of Dutch ancestry)
• Hereditary coproporphyria (HCP)
A 32-year-old man with AIDS presents with melena. The skin lesions illustrated in the figure below are noted. What is the cause of the skin lesions? Could these lesions be responsible for the GI bleeding?
Kaposi’s sarcoma (KS). It is found in up to 10%–15% of HIV-infected individuals.
In the alimentary tract, KS typically occurs as bulky gingival or palatal lesions, or GI lesions resulting in difficulty with chewing, swallowing, and obstruction to flow, respectively.
Rarely, it is a cause of GI bleeding.
A 19-year-old man presents with massive hematochezia and hemodynamic instability. He has no other health problems but does experience recurrent painless skin lesions as shown in the figure below. What is the diagnosis?
Degos’ disease or malignant atrophic papulosis. This is a very rare disorder that affects the skin, GI tract, and central nervous system, and may lead to massive bleeding and death.
What drugs can precipitate an attack of VP?
Inducers of hepatic cytochrome P450 such as barbiturates, dapsone, and estrogens.
What diagnosis should be considered in a patient with dysphagia, heartburn, and fibrotic skin with beaking of the nose, cutaneous telangiectasia, and thinning of the lips?
What does CREST stand for?
• Calcinosis cutis
• Raynaud’s phenomenon
• Esophageal dysmotility
Patients with Ehlers–Danlos syndrome (EDS) are at high risk for what GI problems?
Patients with type IV (arterial subtype) EDS that exhibit hyperextensibility, skin fragility, and the formation of hypertrophic scars are at risk for rupture of the large intestine and/or rupture of the mesenteric arteries in the abdomen. Hernias and diverticula with associated GI bleeding may also be seen.
Yellowish papules in flexural skin and rectal mucosa giving a “plucked chicken” appearance, ocular angioid streaks, hypertension, and GI hemorrhage are suggestive of what disorder?
Pseudoxanthoma elasticum. Other findings may include retinal hemorrhage and detachment, claudication, angina pectoris, abdominal angina, and urinary tract bleeding.
What GI symptoms are commonly seen in patients with cutis laxa?
Hernias (inguinal, umbilical, and obturator), diverticula of the GI tract, and chronic diarrhea.
What conditions with dermatologic manifestations are associated with GI bleeding?
• Hereditary hemorrhagic telangiectasia
• Blue rubber bleb nevus syndrome
• Ehlers–Danlos syndrome
• Pseudoxanthoma elasticum
• Kaposi’s sarcoma (human herpes virus 8)
• Vasculitides (Henoch–Schoenlein disease and polyarteritis nodosa)
• Dego’s disease (malignant atrophic papulosis)
What conditions are associated with both GI polyps and dermatologic manifestations?
• Gardner’s syndrome (associated with multiple epidermal inclusion cysts, lipomas, osteomas of the face, GI adenomas)
• Peutz–Jegher’s syndrome (associated with freckling around the mouth and on the lips, benign GI hamartomas)
• Cronkhite–Canada syndrome (associated with patchy alopecia, nail changes and inflammatory polyps of the stomach and bowel)
• Neurofibromatosis or Von Recklinghausen’s syndrome, type I (associated with axillary and inguinal freckling, café au lait spots, and neurofibromas of the skin and gut)
• Cowden’s disease (an autosomal disorder associated with multiple tricholemmomas [resembling warts] around the mouth, nose and ears, colon polyps, abnormalities of the thyroid, and breast)
What skin signs may aid in the diagnosis of acute hemorrhagic pancreatitis?
• Cullen’s sign (periumbilical ecchymosis)
• Grey Turner’s sign (flank ecchymosis)
What cutaneous signs may herald an underlying GI malignancy?
• Dermatomyositis in adults over 50—associated with gastric and colonic carcinomas.
• Acanthosis nigricans—paraneoplastic variant presents with warty thickening of mouth and palms (“tripe hands”) and is associated with adenocarcinoma of the stomach and bowel.
• Sister Mary Joseph nodule (umbilical metastasis)—associated with carcinoma of the stomach, colon, and ovary.
• Muir–Torre syndrome—autosomal dominant disorder presenting with multiple sebaceous tumors is associated with colon cancer.
• The sign of Leser–Trélat (controversial)—sudden onset of multiple, pruritic seborrheic keratoses has been reported to occur with malignancy of the stomach, breast, prostate, lung, and colon.
• Acrokeratosis of Bazex—symmetrical psoriaform eruption affecting the hands, feet, ears, and nose, seen predominantly in males, and is associated with tumors of the pharynx, esophagus, tongue, and lungs.
• Erythema gyratum repens—a raised, erythematous, concentric eruption that migrates on the skin and is likened to a “wood grain” pattern has been associated with tumors of the breast, lung, bladder, prostate, cervix, stomach, esophagus, and multiple myeloma.
• Ataxia telangiectasia—oculocutaneous telangiectasia, xerosis, gray hair, atrophic or sclerotic skin, recurrent impetigo with progressive cerebellar ataxia and an increased incidence of tumors of the oral cavity, breast, stomach, and pancreas.
• Sweet’s syndrome (acute febrile neutrophilic dermatosis)—erythematous to bluish papules or nodules that coalesce to form well-demarcated plaques, likened to a “relief of a mountain range.” Twenty percent of cases are associated with malignancy. Most commonly seen with acute myelocytic leukemia, it has also been reported to occur with gastric carcinoma and adenocarcinoma of the rectum.
• Acquired ichthyosis—excessively dry skin with tessellated or tile-like scale predominantly on the lower extremities can be seen in many underlying gut tumors but most commonly is associated with lymphoma.
What cutaneous differences occur in the carcinoid syndrome depending on where the tumor originates in relation to the embryologic foregut, midgut, and hindgut?
• Foregut tumors (bronchus, stomach, pancreas) produce serotonin and histamine leading to peptic ulcer disease, brighter and more persistent flushing reactions, lacrimation, sweating, vomiting, and asthma.
• Midgut tumors (small intestine to midcolon) are associated with a bluish flushing with mixed erythema and pallor, hypotension, and bronchoconstriction.
• Hindgut tumors (descending colon and rectum) are not associated with flushing or other manifestations of carcinoid syndrome.
What conditions should be considered in a patient with a painful, erythematous nodule of the lower extremity and known IBD?
• Pyoderma gangrenosum (PG) begins as a painful nodule or pustule then develops into an ulcer with a serpiginous, erythematous to violaceous border and boggy, necrotic base and may not resolve once the bowel disease is under control. PG is more common in patients with ulcerative colitis than Crohn’s disease and may also occur in patients with chronic active hepatitis, diverticulitis, primary biliary cirrhosis, gastric and duodenal ulcers, rheumatoid arthritis, myeloma, and collagen-vascular diseases.
• Erythema nodosum lesions are erythematous, painful nodules that occur predominantly on the extensor surfaces of the lower extremities and may precede the onset of IBD. EN is more common in patients with ulcerative colitis than Crohn’s disease and may also be seen in patients with sarcoidosis, bacterial, viral, acid fast bacilli (AFB) and fungal infections, Behçet’s, oral contraceptive use, and lymphoma.
What GI condition is associated with dermatitis herpetiformis?
Gluten-sensitive enteropathy (ie, celiac disease).
What treatment options are available for dermatitis herpetiformis?
• Gluten-free diet (will resolve intestinal and skin lesions)
• Dapsone (skin lesions respond more rapidly to medications)
• Sulfapyridine (in dapsone-intolerant patients)
What GI manifestations may be seen in patients with urticaria pigmentosa?
Gastric hypersecretion due to elevated plasma histamine leading to gastritis, peptic ulcer disease, diarrhea, abdominal pain, malabsorption in 30% of patients, and abnormal liver tests, in particular alkaline phosphatase.
What skin changes may be seen in patients with primary biliary cirrhosis?
• Melanosis, predominantly in exposed areas
• Scleroderma-associated features
• Lichen planus
• Excoriations from itching
• Xanthomas on the hands feet and trunk, xanthelasma, and occasionally tuberous xanthomas
What skin changes may be seen in patients with Wilson’s disease?
• Azure lunulae or bluish color of the lunular area of the nails
• Kayser–Fleischer rings of the cornea
Where is the most common GI site of involvement in metastatic malignant melanoma?
Small bowel. Nevertheless, malignant melanoma may metastasize anywhere in the GI tract, pancreas, and liver. Primary melanoma may also arise anywhere along the GI tract, often presenting with GI bleeding.
What cutaneous side effects have been seen with anti-TNF-α therapy?
• Lichenoid skin eruptions
• Atopic dermatitis
What GI manifestations may be seen in primary systemic amyloidosis?
• Petechiae, purpura, ecchymoses spontaneously or after minor trauma on the skin, and oral cavity (most common)
• Waxy, smooth papules, nodules, and plaques (skin and oral cavity)
• Macroglossia with or without nodularity
• Chronic intestinal pseudoobstruction
• GI hemorrhage
• Gastric carcinoma
• Diarrhea, malabsorption, and protein-losing enteropathy
What potentially fatal dermatologic condition can occur in a patient with a glomerular filtration rate (GFR) < 30 mL/min who has a magnetic resonance imaging study with contrast?
Nephrogenic systemic fibrosis typically presents with progressive fibrosis of the skin that is both pruritic and painful. It can involve multiple organs including the liver, lung, skeletal muscle, and heart, and is associated with gadolinium use in patients with renal failure.
What GI disorder has been linked to the use of isotretinoin (Accutane)?
IBD. A true causal link has not yet been proven; however, recent epidemiological evidence suggests a strong association between the use of isotretinoin and ulcerative colitis. The association between isotretinoin and Crohn’s disease appears to be less strong. While the potential causal relationship is controversial, large jury settlements have been made to isotretinoin users who developed IBD.
• • • SUGGESTED READINGS • • •
Marks J. The Relationship of Gastrointestinal Disease and the Skin. Clinics in Gastroenter. 1983;12(3):693-712.
Johnston GA, Graham-Brown RAC. The Skin and Disorders of the Alimentary Tract, the Hepatobiliary System, Kidney, and Cardiopulmonary System. In: Wolff K, Goldsmith L, Katz S, et al, eds. Fitzpatrick’s Dermatology in General Medicine. 7th ed, Vol 2. New York: McGraw-Hill; 2007.