SKIN MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE
Crohn’s disease and ulcerative colitis are two common autoimmune gastrointestinal disorders with many cutaneous findings. Most patients do not have the cutaneous findings, but a small proportion of the population with inflammatory bowel disease develop one of the cutaneous manifestations, which include pyoderma gangrenosum, aphthous ulcerations, oral candidiasis, erythema nodosum, metastatic Crohn’s disease, iritis, and conjunctivitis. Arthritis, although not a skin manifestation, can produce red, tender swelling around an afflicted joint space.
|MUCOCUTANEOUS MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE|
Clinical Findings: Ulcerative colitis and Crohn’s disease are more commonly seen in the Caucasian population. Crohn’s disease is slightly more common in women, and ulcerative colitis affects men and women equally. Up to 20% of individuals with inflammatory bowel disease have a family history of the condition. Ulcerative colitis affects the large intestine, whereas Crohn’s disease has been shown to affect any part of the gastrointestinal tract.
Skin manifestations occur in 5% to 10% of those affected by inflammatory bowel disease. The most common skin finding is erythema nodosum. Erythema nodosum manifests as tender dermal nodules predominantly on the shin region. They typically are symmetric in location. There are many associations with erythema nodosum in addition to inflammatory bowel disease, including pregnancy, use of birth control medications, sarcoidosis, deep fungal infections such as coccidiomycosis, and an idiopathic form. The etiology and pathogenesis are unknown. Erythema nodosum can occur in areas other than the pretibial region, but this is uncommon.
Pyoderma gangrenosum is one of the most severe skin manifestations of inflammatory bowel disease. It can manifest as a small, red papule or pustule that can rapidly expand to form a large ulceration with a violaceous undermined rim. The ulcer may form in a cribriform pattern. The skin involved develops small cribriform ulcerations centrally that expand outward and coalesce into one large ulcer. These ulcers are extremely tender and cause significant morbidity. Pyoderma gangrenosum can also be seen as an idiopathic finding or in association with an underlying malignancy, typically in the lymphoproliferative group of malignancies. It has been estimated that approximately 1% of patients with inflammatory bowel disease will develop pyoderma gangrenosum.
Aphthous ulcers can occur anywhere within the oral mucosa. They are shallow ulcerations with a white fibrinous base. They are quite tender and can cause patients to avoid eating because of the severe discomfort. Oral candidiasis is typically an iatrogenic manifestation of inflammatory bowel disease. Most patients are prescribed systemic steroids to treat their underlying disease, and this predisposes them to the development of Candida infections, both oral and vaginal.
Arthritis is seen in approximately 10% of patients with inflammatory bowel disease and is considered to be in the seronegative classification of inflammatory arthropathies.
Metastatic Crohn’s disease is unique to Crohn’s. It represents the spread of the granulomatous disease onto the skin. It most commonly occurs in areas with close approximation to the gastrointestinal tract, such as the perianal and perioral regions. It manifests as tender, draining papules and nodules. A peculiar variant has been described to occur along the inguinal creases. It appears as fissures or ulcerations that can penetrate deeply into the dermis and even the subcutaneous fat tissue. It has been described as slit-like or knife-like linear ulcerations. Isolated genital swelling is another unusual presentation of metastatic Crohn’s disease. Metastatic Crohn’s disease has been described in many other cutaneous locations. This form of cutaneous disease can be difficult to treat.
Other rare skin findings that have been seen in association with inflammatory bowel disease are skin fistulas, vasculitis including polyarteritis nodosa, urticaria, Sweet’s syndrome, epidermolysis bullosa acquisita, and psoriasis.
|CUTANEOUS MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE|
Pathogenesis: The pathogenesis of these cutaneous manifestations of inflammatory bowel disease is unknown. They are theorized to be caused by an autoimmune mechanism of defective cell-mediated immunity. Metastatic Crohn’s disease is believed to be caused when the inflammatory bowel disease recognizes the skin as gut tissue and develops the same granulomatous process within the cutaneous structures.
Histology: Pyoderma gangrenosum shows non-specific ulceration when biopsied. The findings are nondiagnostic, and the diagnosis is one of exclusion. The presence of multiple neutrophils leads one to look for cutaneous infection, and appropriate tissue cultures should be performed and found negative before a diagnosis of pyoderma gangrenosum is made. The appearance of pyoderma gangrenosum histologically is highly dependent on the time and type of lesion biopsied. Early lesions show a follicle-centered neutrophilic infiltrate with a dermal abscess. As the lesions progress, ulceration is seen with a predominant neutrophilic infiltrate. The ulcers are often very deep and enter the subcutaneous tissue. Changes of vasculitis can often be seen, but they are believed to be caused by the overlying ulceration; the vasculitis is not thought to be the predominant pathological process.
Biopsy specimens of erythema nodosum shows a septal panniculitis. The fibrous septa are inflamed with a mixed inflammatory infiltrate with heavy lymphocyte predominance. Giant cells are frequently seen within the widened septal tissue. A unique finding is that of Miescher’s radial granuloma formation, in which multiple histiocytes are arranged flanking a small area. They are organized circumferentially around a central slit-like space. The reason for this finding is unknown. Erythema nodosum is the most common form of septal panniculitis.
Aphthous ulcerations, if biopsied, show small ulcerations or erosions of the mucosa. The predominant cell type found within the infiltrate is the neutrophil. These findings are nonspecific.
Oral candidiasis should be diagnosed without a skin biopsy. A scraping of the white oral plaques shows an easily removed, whitish, sticky tissue. A microscopic examination shows candidal elements. Examination of the biopsy specimen shows the candidal organisms on the surface of the mucosa, with an underlying mixed inflammatory infiltrate.
Metastatic Crohn’s disease is a unique phenomenon. It is histologically described as noncaseating granulomas. These granulomas are identical to the bowel granulomas. The skin granulomas are centered in the dermis but can be seen around blood vessels and into the adipose tissue.
Treatment: Therapy is aimed at controlling the underlying bowel disease. If it is well controlled, the skin manifestations typically follow in line. Conversely, if the bowel disease is poorly controlled, one can expect the skin disease to be poorly controlled as well. It is useful to use the skin manifestations as a sign of active bowel disease. If a patient who has been in a long remission suddenly develops pyoderma gangrenosum, it is highly plausible that the bowel disease has become active once more. Ulcerative colitis can be cured by colectomy. Crohn’s disease cannot be cured by colectomy because it affects the entire gastrointestinal tract. Oral or intravenous immunosuppressive medications are used to treat both these conditions. Oral prednisone, sulfasalazine, azathioprine, methotrexate, myco- phenolate mofetil, and intravenous infliximab have shown excellent results in patients with these chronic diseases. They also have the added benefit of helping the skin disease. Cyclosporine and prednisone have shown excellent results in treating pyoderma gangrenosum. Intralesional triamcinolone can be attempted on small, early lesions of pyoderma gangrenosum.
Oral aphthous ulcers can be treated with topically applied steroid gels or ointments compounded in dental paste formula to increase adherence to the mucosa. Topical anesthetics are commonly used.
Erythema nodosum can be treated with compression stockings, topical potent steroids, and oral steroids in severe cases. Intralesional injection of triamcinolone is also effective. Metastatic Crohn’s disease is difficult to treat and requires systemic immunosuppressive agents such as azathioprine, prednisone, or infliximab. It is best treated by a multi-disciplinary approach.