Gastrointestinal Diseases
Patients with any of a number of gastrointestinal diseases may present with cutaneous manifestations; similarly, patients with certain cutaneous diseases can develop gastrointestinal complications.
Figure 7 Aphthous stomatitis is a common finding in patients with ulcerative colitis.
Figure 8 Pyoderma gangrenosum is characterized by ulcers that begin with craterlike holes draining pus.
Figure 8 Pyoderma gangrenosum is characterized by ulcers that begin with craterlike holes draining pus.
Figure 9 The patient’s nose and cheeks are covered with small papules called trichilemmomas, which represent the cutaneous hallmark of Cowden disease.
Carcinoid syndrome
The carcinoid syndrome is characterized by episodic flushing that can be associated with abdominal pain, diarrhea, and wheezing. Ninety percent of carcinoid tumors originate in the gastrointestinal tract; however, bronchial carcinoids occur occasionally. Less common cutaneous manifestations of carcinoid tumors include sclerodermatous changes. Cutaneous metas-tases present as deep nodules; hyperkeratosis may occur; and the patient may experience pigmentation changes similar to those seen in pellagra.
Inflammatory bowel disease
There are several specific and nonspecific cutaneous manifestations of inflammatory bowel disease [see 4:IV Inflammatory Bowel Diseases]. In both Crohn disease and ulcerative colitis, disease can progress to a hypercoagulable stage, causing venous and arterial thromboses that can lead to loss of digits and limbs. Aphthous stomatitis is another nonspecific manifestation of in-flammatory bowel disease [see Figure 7]. In patients with Crohn disease, the lesions may appear as noncaseating granulomas, whereas in patients with ulcerative colitis, they may be indistinguishable from canker sores.
Figure 10 The primary lesions of herpetiformis are vesicles that quickly break to form crusts and erosions.
Pyoderma gangrenosum occurs in patients with Crohn disease and ulcerative colitis and has also been reported in patients with chronic active hepatitis, rheumatoid arthritis, and a number of myeloproliferative disorders. The lesions are distinguishable from other ulcers by the presence of craterlike holes, pustules, and purulent drainage [see Figure 8]. Pyoderma gangrenosum may occur at sites of trauma. Treatment with intralesionally injected or systemic corticosteroids may be required. Immunosup-pressive agents such as cyclosporine have proved to be dramatically effective; in refractory cases, thalidomide has been shown to be beneficial.27 Infliximab has proved to be highly effective in the treatment of refractory pyoderma gangrenosum.28
Erythema nodosum is a septal panniculitis that is associated with a number of conditions, including Crohn disease, ulcera-tive colitis, Behcet syndrome, sarcoidosis, infection, and the ingestion of estrogens and other drugs. Other manifestations of Crohn disease include inguinal abscesses and sinuses and anal fistulas.
Metastatic crohn disease
The term metastatic Crohn disease refers to histologically proven noncaseating granulomas that are remote from the gastrointestinal tract in patients with Crohn disease. The clinical presentation can be quite variable, and the diagnosis of this disorder is frequently missed. In some cases, patients present with marked swelling of the scrotum or vulva.
Cutaneous conditions with gastrointestinal complications
Cowden Disease
Cowden disease is an autosomal dominant disorder in which gastrointestinal polyps develop along with numerous skin lesions. This disease has been attributed to mutations of the tumor suppressor gene PTEN.29 Wartlike papules known as trichilem-momas occur, particularly around the nose, mouth, and ears but also on the hands and feet [see Figure 9]. Small papules can also develop on the gingival mucosa, creating a cobblestone appearance. Hemangiomas and lipomas can occur.30 A distinctive nodule of the scalp known as Cowden fibroma has been described. Up to 50% of women with Cowden disease develop breast cancer, a finding that has been associated independently with the PTEN mutation.31 Thyroid carcinomas, thyroid adenomas, and thyroid goiters can occur as well.
Dermatitis Herpetiformis
Dermatitis herpetiformis is an immunobullous disease that is associated with a gluten-sensitive enteropathy [see 2:IX Vesiculo-bullous Diseases]. Skin lesions begin as vesicles that are so pruritic that they are quickly broken by scratching, leaving only excoriations and crusts [see Figure 10]. Like patients with celiac disease who are not on a gluten-free diet, patients with dermatitis her-petiformis have an increased risk of gastrointestinal lymphoma.32
Peutz-Jegher Syndrome
In Peutz-Jegher syndrome, patients develop hamartomatous polyps of the small intestine that are associated with pigmented macules of the lips and oral mucosa [see 2:X Malignant Cutaneous Tumors]. Also, pigmented macules can develop on the palms, fingers, soles, and toes and in areas around the mouth, nose, and rectum. The disease is inherited as an autosomal dominant trait, and a significant proportion of cases are associated with mutations in the serine/threonine protein kinase I1/LKB1 (STKI1/ LKB1) gene, although mutations in this gene do not account for all cases.33
Recessive Dystrophic Epidermolysis Bullosa
Recessive dystrophic epidermolysis bullosa is a congenital bullous disease with recurrent blistering and scarring, particularly on the hands and feet [see 2:IX Vesiculobullous Diseases]. The scarring results in pseudosyndactyly, giving rise to mittenlike hands. Ingestion of coarse food can result in mucosal bul-lae of the esophagus, which heal with scarring and stricture formation. Dysphagia is a frequent complaint. Scarring of the esophagus can lead to squamous cell carcinoma, which is a leading cause of death in this disorder.34 Gastroenterologists and dermatologists must play key roles in the management of these patients. Liquid and pureed diets and appropriate skin care are essential to the survival of patients with this debilitating disorder. Prenatal diagnosis can be made by sampling DNA from the chorionic villus.35 All forms of dystrophic epi-dermolysis bullosa have been attributed to mutations in the type VII collagen gene.36 Recently, through the use of a self-inactivating minimal lentivirus-based vector, the type VII collagen gene has been delivered and type VII collagen expressed in immunodeficient mice, suggesting the possibility that, in the future, gene therapy may be available to successfully treat this devastating disorder.37
Hematologic Diseases amyloidosis
There are several forms of local and systemic amyloidosis [see 12:XV Chronic Lymphoid Leukemias and Plasma Cell Disorders]. In a form associated with multiple myeloma, amyloid fibrils consisting of immunoglobulin light chains are deposited in the skin. Shiny translucent papules develop, particularly on the eyelids.
Because of amyloid deposits in blood vessels, spontaneous bleeding occurs. Minimal trauma results in petechiae and pur-pura. Macroglossia also occurs in some patients with myeloma-associated amyloidosis and in some with primary systemic amyloidosis. The systemic manifestations of myeloma-associated and primary systemic amyloidosis are quite varied. Hepatomegaly develops in 50% of patients. Amyloid can affect the heart, resulting in heart failure or myocardial infarction. Survival of patients who undergo heart transplantations for cardiac amyloidosis is lower than survival after cardiac transplantation for other indications.38 Amyloidosis of the gastrointestinal tract can result in malabsorption and protein-losing enteropathy. Treatment with thalidomide (up to 400 mg daily) and intermittent dexamethasone is rapidly effective in some patients, but side effects are frequent.39
Mastocytosis
Mastocytosis is caused by the infiltration of mast cells into the skin and other organs [see 4:X1 Diseases Producing Malabsorption and Maldigestion]. Urticaria pigmentosa refers to the skin lesions that occur in most patients with mastocytosis. Reddish-brown macules and papules resembling nevi are characteristic [see Figure 11]. Stroking of individual lesions results in urticarial wheals—a phenomenon known as the Darier sign. Pruritus, flushing, abdominal pain, nausea, vomiting, and diarrhea are common complaints.
Most patients with mastocytosis have an indolent form of the disease, even when mast cells have infiltrated the bone mar-row.40 Malignant or aggressive systemic mast cell disease can involve the spleen, liver, and lymph nodes in addition to the skin and bone marrow. Histologically, infiltrates contain atypical nonmetachromatic mast cells that are monoclonal in some pa-tients.41 Children with urticaria pigmentosa usually have a better prognosis than adults with the disease.42
The diagnosis of mastocytosis is made by the demonstration of mast cells on skin biopsy. Because mast cells easily degranu-late, making them difficult to identify, biopsies should be performed with a minimum of tissue manipulation.
Porphyrias
The porphyrias result from defective hemoglobin synthesis, leading to excess porphyrins in the blood and in body tissues [see 9:V The Porphyrias].
Figure 11 Multiple brown macules resembling nevi occur in patients with urticaria pigmentosa.
Congenital Erythropoietic Porphyria
Congenital erythropoietic porphyria is a rare autosomal recessive disorder that has been attributed to mutations in the gene for uroporphyrinogen III synthase.43 This condition is characterized by severe photosensitivity. Vesicles and bullae develop after sun exposure; these lesions heal with scar formation. Eryth-rodontia (red-stained teeth) is a characteristic feature [see Figure 12]. Digit, ear, and nose loss is common in patients who manage to survive to adulthood [see Figure 13]. Hypertrichosis is another frequent complication. Formation of gallstones, splenomegaly, and hemolytic anemia are also associated with this condition.
Porphyria Cutanea Tarda
Porphyria cutanea tarda is characterized by photosensitivity, vesicle formation (especially on the dorsa of the hands) [see Figure 14], and hypertrichosis. The condition may be associated with ingestion of alcohol or medications such as estrogens. Diagnosis of the porphyrias can be established by elevated urinary por-phyrin levels. Examination of the urine with a Wood lamp will often reveal pink-red fluorescence attributable to the high level of urinary porphyrins. Porphyria cutanea tarda can be associated with hepatitis C. Phlebotomy is effective therapy.
Immunodeficiency Diseases
Aids
AIDS may result in cutaneous infections and neoplasms that are often dramatic in their extent and severity. This section focuses on selected cutaneous manifestations of infections and other diseases associated with AIDS. (For a more comprehensive discussion of disorders associated with HIV infection, see 7:XXX1II HIV and AIDS and other topics devoted to specific conditions.)
Opportunistic Infections
Viral infections Banal viral infections, such as molluscum contagiosum, that are ordinarily self-limited and easily curable have become widespread, chronic, and enormous problems in patients with AIDS. These umbilicated white papules, ordinarily only a few millimeters in diameter, can reach diameters of 1 to 2 cm in patients with AIDS. Similarly, condyloma acuminatum, caused by human papillomavirus (HPV) infection, is often difficult to treat in patients with AIDS.
Herpes simplex virus infections become chronic and erosive, forming large, nonhealing ulcers [see 7:XXVI Herpesvirus Infections]. Acyclovir-resistant strains of herpes simplex virus have been reported in some patients with AIDS44; these patients require other antiviral agents, such as foscarnet. Mutations in thymidine kinase and DNA polymerase genes of herpes simplex viruses can render them resistant to acyclovir and foscar-net.45 Topical cidofovir gel has been reported to be beneficial for herpes infections in patients infected with HIV.46
Herpes zoster infections are a common sign of HIV infection. In the non-HIV-infected host, herpes zoster is characterized by grouped vesicles in a dermatomal distribution. The eruption is self-limited, resolving within 1 to 2 weeks. In contrast, herpes zoster infection can develop into a disseminated vesicular eruption in patients with AIDS; and in some AIDS patients, chronic herpetic lesions develop and last for months.
Fungal infections Fungal infections are common in patients with HIV infection.
Figure 12 A reddish pigmentation (erythrodontia) occurs when porphyrins are deposited in the teeth in congenital erythropoietic porphyria.
Figure 13 Skin changes in congenital erythropoietic porphyria can be severe; scarring and loss of digits are common in older patients.
Monilial infections include oral thrush and candidiasis of the groin. Several fungal infections that rarely cause widespread infection in patients with normal immune systems (e.g., cryptococcosis, histoplasmosis, aspergillosis, and sporotrichosis) have emerged as serious pathogens in patients with AIDS.
Bacterial infections Bacterial infections are more frequent and severe in patients with AIDS than in patients with normal immune systems. Bacillary angiomatosis, caused by Bartonella henselae, presents as purple papules and nodules that can be mistaken for Kaposi sarcoma (see below). Chronic fever and chills can occur, as can bone lesions. Epidemiologic evidence suggests that cats may be the source of human infection.47 Diagnosis by serologic testing has been commonly used, but in the future, polymerase chain reaction may offer a rapid and convenient way of establishing this diagnosis.48 The condition resolves upon treatment with oral antibiotics [see 7:XI Infections Due to Brucella, Francisella, Yersinia pestis, and Bartonella].
Scabies and other pruritic eruptions Scabies, a severely pruritic eruption, has a predilection for the buttocks, the genitals, the periumbilical area, and the webs between the fingers. Norwegian scabies, a thickly crusted psoriasislike form of the parasitic disease, has been described in patients with Down syndrome and in other immunosuppressed persons. In recent years, Norwegian scabies has been reported most commonly in patients with AIDS. The scales of Norwegian scabies contain thousands of mites that are easily seen with the microscope. Burrows form linear lesions up to 1 cm long. The causative mite, Sarcoptes scabiei, can be identified by microscopic examination of scrapings from the burrows.
Eosinophilic pustular folliculitis and papular eruption of AIDS are pruritic rashes that affect patients with HIV infection. It has been suggested that pruritic papular eruption in patients with HIV infection may represent a reaction to arthropod bites.49
Figure 14 Crusting and scarring follow the appearance of vesicles and bullae in porphyria cutanea tarda.
Figure 15 Kaposi sarcoma is the most common malignancy of AIDS patients. It often presents as purple patches, plaques, or papules. Purple macules on the foot can be seen in patients with classic Kaposi sarcoma but are seen here in a patient with AIDS-related Kaposi sarcoma.
Both eosinophilic pustular folliculitis and papular eruption of AIDS are characterized by severe itching, and skin-colored papules and excoriations are common in both. Patients with eosinophilic pustular folliculitis can develop pustules and ery-thematous papules. Both conditions respond to treatment with ultraviolet B.
